Jun Wang, PhD

Dr. Jun Wang is a tenured Associate Professor in the Department of Pediatrics at McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth Houston). She received her PhD degree from the Texas A&M University Health Science Center in 2010. After completing postdoctoral training at Baylor College of Medicine and serving as an Assistant Professor there, Dr. Wang joined the UTHealth Houston faculty in 2018. Her lab’s research is primarily focused on the molecular and genetic regulation of cardiovascular and craniofacial development, diseases, and regeneration. Her group uses a combination of various experimental approaches including mouse genetics, physiology studies, genome editing, and next-generation sequencing techniques. She has received many honors and awards during her career such as the Lawrence Bone Research Award, an American Heart Association National Career Development Award, a National Institutes of Health (NIH) K01 Award, The University of Texas System Rising STARs Award, and the McGovern Medical School’s Women Faculty Forum Rising Star Award.

See Publications

Education

  • Postgraduate:

    Texas A&M Health Science Center (PhD)

  • Fellowships:

    Baylor College of Medicine

Publications

4862227 AMEMBFXC 1 alternatives-to-animal-experimentation 10 date desc Wang 43829 https://www.texasheart.org/wp-content/plugins/zotpress/
%7B%22status%22%3A%22success%22%2C%22updateneeded%22%3Afalse%2C%22instance%22%3Afalse%2C%22meta%22%3A%7B%22request_last%22%3A0%2C%22request_next%22%3A0%2C%22used_cache%22%3Atrue%7D%2C%22data%22%3A%5B%7B%22key%22%3A%22EDMLJPIL%22%2C%22library%22%3A%7B%22id%22%3A4862227%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Zheng%20et%20al.%22%2C%22parsedDate%22%3A%222023-07%22%2C%22numChildren%22%3A1%7D%2C%22bib%22%3A%22%26lt%3Bdiv%20class%3D%26quot%3Bcsl-bib-body%26quot%3B%20style%3D%26quot%3Bline-height%3A%201.35%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%26quot%3B%26gt%3B%5Cn%20%20%26lt%3Bdiv%20class%3D%26quot%3Bcsl-entry%26quot%3B%26gt%3BZheng%2C%20M.%2C%20Erhardt%2C%20S.%2C%20Cao%2C%20Y.%20et%20al.%20%282023%29.%20Emerging%20signaling%20regulation%20of%20sinoatrial%20node%20dysfunction.%20%26lt%3Bi%26gt%3BCurr%20Cardiol%20Rep%26lt%3B%5C%2Fi%26gt%3B%20%26lt%3Bi%26gt%3B25%26lt%3B%5C%2Fi%26gt%3B%2C%20621%26%23x2013%3B630.%20%26lt%3Ba%20class%3D%26%23039%3Bzp-DOIURL%26%23039%3B%20href%3D%26%23039%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1007%5C%2Fs11886-023-01885-8%26%23039%3B%26gt%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1007%5C%2Fs11886-023-01885-8%26lt%3B%5C%2Fa%26gt%3B.%26lt%3B%5C%2Fdiv%26gt%3B%5Cn%26lt%3B%5C%2Fdiv%26gt%3B%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Emerging%20signaling%20regulation%20of%20sinoatrial%20node%20dysfunction%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mingjie%22%2C%22lastName%22%3A%22Zheng%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Shannon%22%2C%22lastName%22%3A%22Erhardt%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yuhan%22%2C%22lastName%22%3A%22Cao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jun%22%2C%22lastName%22%3A%22Wang%22%7D%5D%2C%22abstractNote%22%3A%22PURPOSE%20OF%20REVIEW%3A%20The%20sinoatrial%20node%20%28SAN%29%2C%20the%20natural%20pacemaker%20of%20the%20heart%2C%20is%5Cu00a0responsible%20for%20generating%20electrical%20impulses%20and%20initiating%20each%20heartbeat.%20Sinoatrial%20node%20dysfunction%20%28SND%29%20causes%5Cu00a0various%20arrhythmias%20such%20as%20sinus%20arrest%2C%20SAN%20block%2C%20and%20tachycardia%5C%2Fbradycardia%20syndrome.%20Unraveling%20the%20underlying%20mechanisms%20of%20SND%20is%20of%20paramount%20importance%20in%20the%20pursuit%20of%20developing%20effective%20therapeutic%20strategies%20for%20patients%20with%20SND.%20This%20review%20provides%20a%20concise%20summary%20of%20the%20most%5Cu00a0recent%20progress%20in%20the%20signaling%20regulation%20of%20SND.%5CnRECENT%20FINDINGS%3A%20Recent%20studies%20indicate%20that%20SND%20can%20be%20caused%20by%20abnormal%20intercellular%20and%20intracellular%20signaling%2C%20various%20forms%20of%20heart%20failure%20%28HF%29%2C%20and%20diabetes.%20These%20discoveries%20provide%20novel%20insights%20into%20the%20underlying%5Cu00a0mechanisms%20SND%2C%20advancing%20our%20understanding%20of%20its%20pathogenesis.%20SND%20can%20cause%20severe%20cardiac%20arrhythmias%20associated%20with%20syncope%20and%20an%20increased%20risk%20of%20sudden%20death.%20In%20addition%20to%5Cu00a0ion%20channels%2C%20the%20SAN%20is%20susceptible%20to%20the%20influence%20of%5Cu00a0various%20signalings%20including%20Hippo%2C%20AMP-activated%20protein%20kinase%20%28AMPK%29%2C%20mechanical%20force%2C%20and%20natriuretic%20peptide%20receptors.%20New%20cellular%20and%20molecular%20mechanisms%20related%20to%20SND%20are%20also%20deciphered%20in%20systemic%20diseases%20such%20as%20HF%20and%20diabetes.%20Progress%20in%20these%20studies%20contributes%20to%20the%20development%20of%20potential%20therapeutics%20for%20SND.%22%2C%22date%22%3A%222023-07%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.1007%5C%2Fs11886-023-01885-8%22%2C%22ISSN%22%3A%221534-3170%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%22AMEMBFXC%22%2C%22Q46ISS7S%22%5D%2C%22dateModified%22%3A%222023-07-21T19%3A10%3A15Z%22%7D%7D%2C%7B%22key%22%3A%226KDFIM2F%22%2C%22library%22%3A%7B%22id%22%3A4862227%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Liao%20et%20al.%22%2C%22parsedDate%22%3A%222023-05-19%22%2C%22numChildren%22%3A1%7D%2C%22bib%22%3A%22%26lt%3Bdiv%20class%3D%26quot%3Bcsl-bib-body%26quot%3B%20style%3D%26quot%3Bline-height%3A%201.35%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%26quot%3B%26gt%3B%5Cn%20%20%26lt%3Bdiv%20class%3D%26quot%3Bcsl-entry%26quot%3B%26gt%3BLiao%2C%20Y.%2C%20Xiang%2C%20Y.%2C%20Zheng%2C%20M.%20et%20al.%20%282023%29.%20DeepMiceTL%3A%20a%20deep%20transfer%20learning%20based%20prediction%20of%20mice%20cardiac%20conduction%20diseases%20using%20early%20electrocardiograms.%20%26lt%3Bi%26gt%3BBrief%20Bioinform%26lt%3B%5C%2Fi%26gt%3B%20%26lt%3Bi%26gt%3B24%26lt%3B%5C%2Fi%26gt%3B%2C%20bbad109.%20%26lt%3Ba%20class%3D%26%23039%3Bzp-DOIURL%26%23039%3B%20href%3D%26%23039%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1093%5C%2Fbib%5C%2Fbbad109%26%23039%3B%26gt%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1093%5C%2Fbib%5C%2Fbbad109%26lt%3B%5C%2Fa%26gt%3B.%26lt%3B%5C%2Fdiv%26gt%3B%5Cn%26lt%3B%5C%2Fdiv%26gt%3B%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22DeepMiceTL%3A%20a%20deep%20transfer%20learning%20based%20prediction%20of%20mice%20cardiac%20conduction%20diseases%20using%20early%20electrocardiograms%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ying%22%2C%22lastName%22%3A%22Liao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yisha%22%2C%22lastName%22%3A%22Xiang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mingjie%22%2C%22lastName%22%3A%22Zheng%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jun%22%2C%22lastName%22%3A%22Wang%22%7D%5D%2C%22abstractNote%22%3A%22Cardiac%20conduction%20disease%20is%20a%20major%20cause%20of%20morbidity%20and%20mortality%20worldwide.%20There%20is%20considerable%20clinical%20significance%20and%20an%20emerging%20need%20of%20early%20detection%20of%20these%20diseases%20for%20preventive%20treatment%20success%20before%20more%20severe%20arrhythmias%20occur.%20However%2C%20developing%20such%20early%20screening%20tools%20is%20challenging%20due%20to%20the%20lack%20of%20early%20electrocardiograms%20%28ECGs%29%20before%20symptoms%20occur%20in%20patients.%20Mouse%20models%20are%20widely%20used%20in%20cardiac%20arrhythmia%20research.%20The%20goal%20of%20this%20paper%20is%20to%20develop%20deep%20learning%20models%20to%20predict%20cardiac%20conduction%20diseases%20in%20mice%20using%20their%20early%20ECGs.%20We%20hypothesize%20that%20mutant%20mice%20present%20subtle%20abnormalities%20in%20their%20early%20ECGs%20before%20severe%20arrhythmias%20present.%20These%20subtle%20patterns%20can%20be%20detected%20by%20deep%20learning%20though%20they%20are%20hard%20to%20be%20identified%20by%20human%20eyes.%20We%20propose%20a%20deep%20transfer%20learning%20model%2C%20DeepMiceTL%2C%20which%20leverages%20knowledge%20from%20human%20ECGs%20to%20learn%20mouse%20ECG%20patterns.%20We%20further%20apply%20the%20Bayesian%20optimization%20and%20%24k%24-fold%20cross%20validation%20methods%20to%20tune%20the%20hyperparameters%20of%20the%20DeepMiceTL.%20Our%20results%20show%20that%20DeepMiceTL%20achieves%20a%20promising%20performance%20%28F1-score%3A%2083.8%25%2C%20accuracy%3A%2084.8%25%29%20in%20predicting%20the%20occurrence%20of%20cardiac%20conduction%20diseases%20using%20early%20mouse%20ECGs.%20This%20study%20is%20among%20the%20first%20efforts%20that%20use%20state-of-the-art%20deep%20transfer%20learning%20to%20identify%20ECG%20patterns%20during%20the%20early%20course%20of%20cardiac%20conduction%20disease%20in%20mice.%20Our%20approach%20not%20only%20could%20help%20in%20cardiac%20conduction%20disease%20research%20in%20mice%2C%20but%20also%20suggest%20a%20feasibility%20for%20early%20clinical%20diagnosis%20of%20human%20cardiac%20conduction%20diseases%20and%20other%20types%20of%20cardiac%20arrythmias%20using%20deep%20transfer%20learning%20in%20the%20future.%22%2C%22date%22%3A%222023-05-19%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.1093%5C%2Fbib%5C%2Fbbad109%22%2C%22ISSN%22%3A%221477-4054%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%22AMEMBFXC%22%2C%225WVJH2TN%22%5D%2C%22dateModified%22%3A%222023-06-08T13%3A53%3A37Z%22%7D%7D%2C%7B%22key%22%3A%22ETZUGJFA%22%2C%22library%22%3A%7B%22id%22%3A4862227%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Zhong%20et%20al.%22%2C%22parsedDate%22%3A%222023-04%22%2C%22numChildren%22%3A2%7D%2C%22bib%22%3A%22%26lt%3Bdiv%20class%3D%26quot%3Bcsl-bib-body%26quot%3B%20style%3D%26quot%3Bline-height%3A%201.35%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%26quot%3B%26gt%3B%5Cn%20%20%26lt%3Bdiv%20class%3D%26quot%3Bcsl-entry%26quot%3B%26gt%3BZhong%2C%20Y.%2C%20Tang%2C%20K.%2C%20Nattel%2C%20S.%20et%20al.%20%282023%29.%20Myosin%20light-chain%204%20gene-transfer%20attenuates%20atrial%20fibrosis%20while%20correcting%20autophagic%20flux%20dysregulation.%20%26lt%3Bi%26gt%3BRedox%20Biol%26lt%3B%5C%2Fi%26gt%3B%20%26lt%3Bi%26gt%3B60%26lt%3B%5C%2Fi%26gt%3B%2C%20102606.%20%26lt%3Ba%20class%3D%26%23039%3Bzp-DOIURL%26%23039%3B%20href%3D%26%23039%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1016%5C%2Fj.redox.2023.102606%26%23039%3B%26gt%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1016%5C%2Fj.redox.2023.102606%26lt%3B%5C%2Fa%26gt%3B.%26lt%3B%5C%2Fdiv%26gt%3B%5Cn%26lt%3B%5C%2Fdiv%26gt%3B%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Myosin%20light-chain%204%20gene-transfer%20attenuates%20atrial%20fibrosis%20while%20correcting%20autophagic%20flux%20dysregulation%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yuan%22%2C%22lastName%22%3A%22Zhong%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Kai%22%2C%22lastName%22%3A%22Tang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Stanley%22%2C%22lastName%22%3A%22Nattel%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ming%22%2C%22lastName%22%3A%22Zhai%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Shiyu%22%2C%22lastName%22%3A%22Gong%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Qing%22%2C%22lastName%22%3A%22Yu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yanxi%22%2C%22lastName%22%3A%22Zeng%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Guangxi%22%2C%22lastName%22%3A%22E%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Nuerbiyemu%22%2C%22lastName%22%3A%22Maimaitiaili%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jun%22%2C%22lastName%22%3A%22Wang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yawei%22%2C%22lastName%22%3A%22Xu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Wenhui%22%2C%22lastName%22%3A%22Peng%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Hailing%22%2C%22lastName%22%3A%22Li%22%7D%5D%2C%22abstractNote%22%3A%22OBJECTIVES%3A%20To%20determine%20the%20role%20of%20MYL4%20regulation%20of%20lysosomal%20function%20and%20its%20disturbance%20in%20fibrotic%20atrial%20cardiomyopathy.%5CnBACKGROUND%3A%20We%20have%20previously%20demonstrated%20that%20the%20atrial-specific%20essential%20light%20chain%20protein%20MYL4%20is%20required%20for%20atrial%20contractile%2C%20electrical%2C%20and%20structural%20integrity.%20MYL4%20mutation%5C%2Fdysfunction%20leads%20to%20atrial%20fibrosis%2C%20standstill%2C%20and%20dysrhythmia.%20However%2C%20the%20underlying%20pathogenic%20mechanisms%20remain%20unclear.%5CnMETHODS%20AND%20RESULTS%3A%20Rats%20subjected%20to%20knock-in%20of%20a%20pathogenic%20MYL4%20mutant%20%28p.E11K%29%20developed%20fibrotic%20atrial%20cardiomyopathy.%20Proteome%20analysis%20and%20single-cell%20RNA%20sequencing%20indicate%20enrichment%20of%20autophagy%20pathways%20in%20mutant-MYL4%20atrial%20dysfunction.%20Immunofluorescence%20and%20electron%20microscopy%20revealed%20undegraded%20autophagic%20vesicles%20accumulated%20in%20MYL4p.E11K%20rat%20atrium.%20Next%2C%20we%20identified%20that%20dysfunctional%20MYL4%20protein%20impairs%20autophagy%20flux%20in%20vitro%20and%20in%20vivo.%20Cardiac%20lysosome%20positioning%20and%20mobility%20were%20regulated%20by%20MYL4%20in%20cardiomyocytes%2C%20which%20affected%20lysosomal%20acidification%20and%20maturation%20of%20lysosomal%20cathepsins.%20We%20then%20examined%20the%20effects%20of%20MYL4%20overexpression%20via%20adenoviral%20gene-transfer%20on%20atrial%20cardiomyopathy%20induced%20by%20MYL4%20mutation%3A%20MYL4%20protein%20overexpression%20attenuated%20atrial%20structural%20remodeling%20and%20autophagy%20dysfunction.%5CnCONCLUSIONS%3A%20MYL4%20regulates%20autophagic%20flux%20in%20atrial%20cardiomyocytes%20via%20lysosomal%20mobility.%20MYL4%20overexpression%20attenuates%20MYL4%20p.E11K%20induced%20fibrotic%20atrial%20cardiomyopathy%2C%20while%20correcting%20autophagy%20and%20lysosomal%20function.%20These%20results%20provide%20a%20molecular%20basis%20for%20MYL4-mutant%20induced%20fibrotic%20atrial%20cardiomyopathy%20and%20identify%20a%20potential%20biological-therapy%20approach%20for%20the%20treatment%20of%20atrial%20fibrosis.%22%2C%22date%22%3A%222023-04%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.1016%5C%2Fj.redox.2023.102606%22%2C%22ISSN%22%3A%222213-2317%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%22AMEMBFXC%22%2C%22BNSCCUCI%22%5D%2C%22dateModified%22%3A%222023-07-21T18%3A44%3A35Z%22%7D%7D%2C%7B%22key%22%3A%227N89YSI4%22%2C%22library%22%3A%7B%22id%22%3A4862227%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Erhardt%20and%20Wang%22%2C%22parsedDate%22%3A%222022-12-28%22%2C%22numChildren%22%3A2%7D%2C%22bib%22%3A%22%26lt%3Bdiv%20class%3D%26quot%3Bcsl-bib-body%26quot%3B%20style%3D%26quot%3Bline-height%3A%201.35%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%26quot%3B%26gt%3B%5Cn%20%20%26lt%3Bdiv%20class%3D%26quot%3Bcsl-entry%26quot%3B%26gt%3BErhardt%2C%20S.%20and%20%26lt%3Bstrong%26gt%3BWang%26lt%3B%5C%2Fstrong%26gt%3B%2C%20J.%20%282022%29.%20Cardiac%20Neural%20Crest%20and%20Cardiac%20Regeneration.%20%26lt%3Bi%26gt%3BCells%26lt%3B%5C%2Fi%26gt%3B%20%26lt%3Bi%26gt%3B12%26lt%3B%5C%2Fi%26gt%3B%2C%20111.%20%26lt%3Ba%20class%3D%26%23039%3Bzp-DOIURL%26%23039%3B%20href%3D%26%23039%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.3390%5C%2Fcells12010111%26%23039%3B%26gt%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.3390%5C%2Fcells12010111%26lt%3B%5C%2Fa%26gt%3B.%26lt%3B%5C%2Fdiv%26gt%3B%5Cn%26lt%3B%5C%2Fdiv%26gt%3B%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Cardiac%20Neural%20Crest%20and%20Cardiac%20Regeneration%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Shannon%22%2C%22lastName%22%3A%22Erhardt%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jun%22%2C%22lastName%22%3A%22Wang%22%7D%5D%2C%22abstractNote%22%3A%22Neural%20crest%20cells%20%28NCCs%29%20are%20a%20vertebrate-specific%2C%20multipotent%20stem%20cell%20population%20that%20have%20the%20ability%20to%20migrate%20and%20differentiate%20into%20various%20cell%20populations%20throughout%20the%20embryo%20during%20embryogenesis.%20The%20heart%20is%20a%20muscular%20and%20complex%20organ%20whose%20primary%20function%20is%20to%20pump%20blood%20and%20nutrients%20throughout%20the%20body.%20Mammalian%20hearts%2C%20such%20as%20those%20of%20humans%2C%20lose%20their%20regenerative%20ability%20shortly%20after%20birth.%20However%2C%20a%20few%20vertebrate%20species%2C%20such%20as%20zebrafish%2C%20have%20the%20ability%20to%20self-repair%5C%2Fregenerate%20after%20cardiac%20damage.%20Recent%20research%20has%20discovered%20the%20potential%20functional%20ability%20and%20contribution%20of%20cardiac%20NCCs%20to%20cardiac%20regeneration%20through%20the%20use%20of%20various%20vertebrate%20species%20and%20pluripotent%20stem%20cell-derived%20NCCs.%20Here%2C%20we%20review%20the%20neural%20crest%26%23039%3Bs%20regenerative%20capacity%20in%20various%20tissues%20and%20organs%2C%20and%20in%20particular%2C%20we%20summarize%20the%20characteristics%20of%20cardiac%20NCCs%20between%20species%20and%20their%20roles%20in%20cardiac%20regeneration.%20We%20further%20discuss%20emerging%20and%20future%20work%20to%20determine%20the%20potential%20contributions%20of%20NCCs%20for%20disease%20treatment.%22%2C%22date%22%3A%222022-12-28%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.3390%5C%2Fcells12010111%22%2C%22ISSN%22%3A%222073-4409%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%22AMEMBFXC%22%2C%22BNSCCUCI%22%5D%2C%22dateModified%22%3A%222023-07-21T18%3A44%3A16Z%22%7D%7D%2C%7B%22key%22%3A%226IM5TEVB%22%2C%22library%22%3A%7B%22id%22%3A4862227%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Zheng%20et%20al.%22%2C%22parsedDate%22%3A%222022-11-29%22%2C%22numChildren%22%3A1%7D%2C%22bib%22%3A%22%26lt%3Bdiv%20class%3D%26quot%3Bcsl-bib-body%26quot%3B%20style%3D%26quot%3Bline-height%3A%201.35%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%26quot%3B%26gt%3B%5Cn%20%20%26lt%3Bdiv%20class%3D%26quot%3Bcsl-entry%26quot%3B%26gt%3BZheng%2C%20M.%2C%20Li%2C%20R.%20G.%2C%20Song%2C%20J.%20et%20al.%20%282022%29.%20Hippo-Yap%20signaling%20maintains%20sinoatrial%20node%20homeostasis.%20%26lt%3Bi%26gt%3BCirculation%26lt%3B%5C%2Fi%26gt%3B%20%26lt%3Bi%26gt%3B146%26lt%3B%5C%2Fi%26gt%3B%2C%201694%26%23x2013%3B1711.%20%26lt%3Ba%20class%3D%26%23039%3Bzp-DOIURL%26%23039%3B%20href%3D%26%23039%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1161%5C%2FCIRCULATIONAHA.121.058777%26%23039%3B%26gt%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1161%5C%2FCIRCULATIONAHA.121.058777%26lt%3B%5C%2Fa%26gt%3B.%26lt%3B%5C%2Fdiv%26gt%3B%5Cn%26lt%3B%5C%2Fdiv%26gt%3B%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Hippo-Yap%20signaling%20maintains%20sinoatrial%20node%20homeostasis%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mingjie%22%2C%22lastName%22%3A%22Zheng%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Rich%20G.%22%2C%22lastName%22%3A%22Li%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jia%22%2C%22lastName%22%3A%22Song%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Xiaolei%22%2C%22lastName%22%3A%22Zhao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Li%22%2C%22lastName%22%3A%22Tang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Shannon%22%2C%22lastName%22%3A%22Erhardt%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Wen%22%2C%22lastName%22%3A%22Chen%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Bao%20H.%22%2C%22lastName%22%3A%22Nguyen%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Xiao%22%2C%22lastName%22%3A%22Li%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Min%22%2C%22lastName%22%3A%22Li%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jianxin%22%2C%22lastName%22%3A%22Wang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Sylvia%20M.%22%2C%22lastName%22%3A%22Evans%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Vincent%20M.%22%2C%22lastName%22%3A%22Christoffels%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Na%22%2C%22lastName%22%3A%22Li%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jun%22%2C%22lastName%22%3A%22Wang%22%7D%5D%2C%22abstractNote%22%3A%22BACKGROUND%3A%20The%20sinoatrial%20node%20%28SAN%29%20functions%20as%20the%20pacemaker%20of%20the%20heart%2C%20initiating%20rhythmic%20heartbeats.%20Despite%20its%20importance%2C%20the%20SAN%20is%20one%20of%20the%20most%20poorly%20understood%20cardiac%20entities%20because%20of%20its%20small%20size%20and%20complex%20composition%20and%20function.%20The%20Hippo%20signaling%20pathway%20is%20a%20molecular%20signaling%20pathway%20fundamental%20to%20heart%20development%20and%20regeneration.%20Although%20abnormalities%20of%20the%20Hippo%20pathway%20are%20associated%20with%20cardiac%20arrhythmias%20in%20human%20patients%2C%20the%20role%20of%20this%20pathway%20in%20the%20SAN%20is%20unknown.%5CnMETHODS%3A%20We%20investigated%20key%20regulators%20of%20the%20Hippo%20pathway%20in%20SAN%20pacemaker%20cells%20by%20conditionally%20inactivating%20the%20Hippo%20signaling%20kinases%20Lats1%20and%20Lats2%20using%20the%20tamoxifen-inducible%2C%20cardiac%20conduction%20system-specific%20Cre%20driver%20Hcn4CreERT2%20with%20Lats1%20and%20Lats2%20conditional%20knockout%20alleles.%20In%20addition%2C%20the%20Hippo-signaling%20effectors%20Yap%20and%20Taz%20were%20conditionally%20inactivated%20in%20the%20SAN.%20To%20determine%20the%20function%20of%20Hippo%20signaling%20in%20the%20SAN%20and%20other%20cardiac%20conduction%20system%20components%2C%20we%20conducted%20a%20series%20of%20physiological%20and%20molecular%20experiments%2C%20including%20telemetry%20ECG%20recording%2C%20echocardiography%2C%20Masson%20Trichrome%20staining%2C%20calcium%20imaging%2C%20immunostaining%2C%20RNAscope%2C%20cleavage%20under%20targets%20and%20tagmentation%20sequencing%20using%20antibodies%20against%20Yap1%20or%20H3K4me3%2C%20quantitative%20real-time%20polymerase%20chain%20reaction%2C%20and%20Western%20blotting.%20We%20also%20performed%20comprehensive%20bioinformatics%20analyses%20of%20various%20datasets.%5CnRESULTS%3A%20We%20found%20that%20Lats1%5C%2F2%20inactivation%20caused%20severe%20sinus%20node%20dysfunction.%20Compared%20with%20the%20controls%2C%20Lats1%5C%2F2%20conditional%20knockout%20mutants%20exhibited%20dysregulated%20calcium%20handling%20and%20increased%20fibrosis%20in%20the%20SAN%2C%20indicating%20that%20Lats1%5C%2F2%20function%20through%20both%20cell-autonomous%20and%20non-cell-autonomous%20mechanisms.%20It%20is%20notable%20that%20the%20Lats1%5C%2F2%20conditional%20knockout%20phenotype%20was%20rescued%20by%20genetic%20deletion%20of%20Yap%20and%20Taz%20in%20the%20cardiac%20conduction%20system.%20These%20rescued%20mice%20had%20normal%20sinus%20rhythm%20and%20reduced%20fibrosis%20of%20the%20SAN%2C%20indicating%20that%20Lats1%5C%2F2%20function%20through%20Yap%20and%20Taz.%20Cleavage%20Under%20Targets%20and%20Tagmentation%20sequencing%20data%20showed%20that%20Yap%20potentially%20regulates%20genes%20critical%20for%20calcium%20homeostasis%20such%20as%20Ryr2%20and%20genes%20encoding%20paracrine%20factors%20important%20in%20intercellular%20communication%20and%20fibrosis%20induction%20such%20as%20Tgfb1%20and%20Tgfb3.%20Consistent%20with%20this%2C%20Lats1%5C%2F2%20conditional%20knockout%20mutants%20had%20decreased%20Ryr2%20expression%20and%20increased%20Tgfb1%20and%20Tgfb3%20expression%20compared%20with%20control%20mice.%5CnCONCLUSIONS%3A%20We%20reveal%2C%20for%20the%20first%20time%20to%20our%20knowledge%2C%20that%20the%20canonical%20Hippo-Yap%20pathway%20plays%20a%20pivotal%20role%20in%20maintaining%20SAN%20homeostasis.%22%2C%22date%22%3A%22Nov%2029%202022%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.1161%5C%2FCIRCULATIONAHA.121.058777%22%2C%22ISSN%22%3A%221524-4539%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%22L366QQZ6%22%2C%22AMEMBFXC%22%2C%226EZ8LZ9X%22%2C%22QF52JASW%22%5D%2C%22dateModified%22%3A%222023-03-07T21%3A55%3A08Z%22%7D%7D%2C%7B%22key%22%3A%22SW2HVDZ8%22%2C%22library%22%3A%7B%22id%22%3A4862227%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Zhao%20et%20al.%22%2C%22parsedDate%22%3A%222022-10-25%22%2C%22numChildren%22%3A1%7D%2C%22bib%22%3A%22%26lt%3Bdiv%20class%3D%26quot%3Bcsl-bib-body%26quot%3B%20style%3D%26quot%3Bline-height%3A%201.35%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%26quot%3B%26gt%3B%5Cn%20%20%26lt%3Bdiv%20class%3D%26quot%3Bcsl-entry%26quot%3B%26gt%3BZhao%2C%20X.%2C%20Tang%2C%20L.%2C%20Le%2C%20T.%20P.%20et%20al.%20%282022%29.%20Yap%20and%20Taz%20promote%20osteogenesis%20and%20prevent%20chondrogenesis%20in%20neural%20crest%20cells%20in%20vitro%20and%20in%20vivo.%20%26lt%3Bi%26gt%3BSci%20Signal%26lt%3B%5C%2Fi%26gt%3B%20%26lt%3Bi%26gt%3B15%26lt%3B%5C%2Fi%26gt%3B%2C%20eabn9009.%20%26lt%3Ba%20class%3D%26%23039%3Bzp-DOIURL%26%23039%3B%20href%3D%26%23039%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1126%5C%2Fscisignal.abn9009%26%23039%3B%26gt%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1126%5C%2Fscisignal.abn9009%26lt%3B%5C%2Fa%26gt%3B.%26lt%3B%5C%2Fdiv%26gt%3B%5Cn%26lt%3B%5C%2Fdiv%26gt%3B%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Yap%20and%20Taz%20promote%20osteogenesis%20and%20prevent%20chondrogenesis%20in%20neural%20crest%20cells%20in%20vitro%20and%20in%20vivo%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Xiaolei%22%2C%22lastName%22%3A%22Zhao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Li%22%2C%22lastName%22%3A%22Tang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Tram%20P.%22%2C%22lastName%22%3A%22Le%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Bao%20H.%22%2C%22lastName%22%3A%22Nguyen%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Wen%22%2C%22lastName%22%3A%22Chen%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mingjie%22%2C%22lastName%22%3A%22Zheng%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Hiroyuki%22%2C%22lastName%22%3A%22Yamaguchi%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Brian%22%2C%22lastName%22%3A%22Dawson%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Shuangjie%22%2C%22lastName%22%3A%22You%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Idaliz%20M.%22%2C%22lastName%22%3A%22Martinez-Traverso%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Shannon%22%2C%22lastName%22%3A%22Erhardt%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jianxin%22%2C%22lastName%22%3A%22Wang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Min%22%2C%22lastName%22%3A%22Li%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22James%20F.%22%2C%22lastName%22%3A%22Martin%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Brendan%20H.%22%2C%22lastName%22%3A%22Lee%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yoshihiro%22%2C%22lastName%22%3A%22Komatsu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jun%22%2C%22lastName%22%3A%22Wang%22%7D%5D%2C%22abstractNote%22%3A%22Neural%20crest%20cells%20%28NCCs%29%20are%20multipotent%20stem%20cells%20that%20can%20differentiate%20into%20multiple%20cell%20types%2C%20including%20the%20osteoblasts%20and%20chondrocytes%2C%20and%20constitute%20most%20of%20the%20craniofacial%20skeleton.%20Here%2C%20we%20show%20through%20in%20vitro%20and%20in%20vivo%20studies%20that%20the%20transcriptional%20regulators%20Yap%20and%20Taz%20have%20redundant%20functions%20as%20key%20determinants%20of%20the%20specification%20and%20differentiation%20of%20NCCs%20into%20osteoblasts%20or%20chondrocytes.%20Primary%20and%20cultured%20NCCs%20deficient%20in%20Yap%20and%20Taz%20switched%20from%20osteogenesis%20to%20chondrogenesis%2C%20and%20NCC-specific%20deficiency%20for%20Yap%20and%20Taz%20resulted%20in%20bone%20loss%20and%20ectopic%20cartilage%20in%20mice.%20Yap%20bound%20to%20the%20regulatory%20elements%20of%20key%20genes%20that%20govern%20osteogenesis%20and%20chondrogenesis%20in%20NCCs%20and%20directly%20regulated%20the%20expression%20of%20these%20genes%2C%20some%20of%20which%20also%20contained%20binding%20sites%20for%20the%20TCF%5C%2FLEF%20transcription%20factors%20that%20interact%20with%20the%20Wnt%20effector%20%5Cu03b2-catenin.%20During%20differentiation%20of%20NCCs%20in%20vitro%20and%20NCC-derived%20osteogenesis%20in%20vivo%2C%20Yap%20and%20Taz%20promoted%20the%20expression%20of%20osteogenic%20genes%20such%20as%20Runx2%20and%20Sp7%20but%20repressed%20the%20expression%20of%20chondrogenic%20genes%20such%20as%20Sox9%20and%20Col2a1.%20Furthermore%2C%20Yap%20and%20Taz%20interacted%20with%20%5Cu03b2-catenin%20in%20NCCs%20to%20coordinately%20promote%20osteoblast%20differentiation%20and%20repress%20chondrogenesis.%20Together%2C%20our%20data%20indicate%20that%20Yap%20and%20Taz%20promote%20osteogenesis%20in%20NCCs%20and%20prevent%20chondrogenesis%2C%20partly%20through%20interactions%20with%20the%20Wnt-%5Cu03b2-catenin%20pathway.%22%2C%22date%22%3A%22Oct%2025%2C%202022%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.1126%5C%2Fscisignal.abn9009%22%2C%22ISSN%22%3A%221937-9145%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%227IGCL8QC%22%2C%22AMEMBFXC%22%2C%22MDTREPAF%22%5D%2C%22dateModified%22%3A%222023-03-07T21%3A55%3A09Z%22%7D%7D%2C%7B%22key%22%3A%22G5HDVHP5%22%2C%22library%22%3A%7B%22id%22%3A4862227%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Ding%20et%20al.%22%2C%22parsedDate%22%3A%222022-10-18%22%2C%22numChildren%22%3A2%7D%2C%22bib%22%3A%22%26lt%3Bdiv%20class%3D%26quot%3Bcsl-bib-body%26quot%3B%20style%3D%26quot%3Bline-height%3A%201.35%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%26quot%3B%26gt%3B%5Cn%20%20%26lt%3Bdiv%20class%3D%26quot%3Bcsl-entry%26quot%3B%26gt%3BDing%2C%20Y.%2C%20Lang%2C%20D.%2C%20Yan%2C%20J.%20et%20al.%20%282022%29.%20A%20phenotype-based%20forward%20genetic%20screen%20identifies%20%26lt%3Bi%26gt%3BDnajb6%26lt%3B%5C%2Fi%26gt%3B%20as%20a%20sick%20sinus%20syndrome%20gene.%20%26lt%3Bi%26gt%3BElife%26lt%3B%5C%2Fi%26gt%3B%20%26lt%3Bi%26gt%3B11%26lt%3B%5C%2Fi%26gt%3B%2C%20e77327.%20%26lt%3Ba%20class%3D%26%23039%3Bzp-DOIURL%26%23039%3B%20href%3D%26%23039%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.7554%5C%2FeLife.77327%26%23039%3B%26gt%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.7554%5C%2FeLife.77327%26lt%3B%5C%2Fa%26gt%3B.%26lt%3B%5C%2Fdiv%26gt%3B%5Cn%26lt%3B%5C%2Fdiv%26gt%3B%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22A%20phenotype-based%20forward%20genetic%20screen%20identifies%20%3Ci%3EDnajb6%3C%5C%2Fi%3E%20as%20a%20sick%20sinus%20syndrome%20gene%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yonghe%22%2C%22lastName%22%3A%22Ding%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Di%22%2C%22lastName%22%3A%22Lang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jianhua%22%2C%22lastName%22%3A%22Yan%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Haisong%22%2C%22lastName%22%3A%22Bu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Hongsong%22%2C%22lastName%22%3A%22Li%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Kunli%22%2C%22lastName%22%3A%22Jiao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jingchun%22%2C%22lastName%22%3A%22Yang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Haibo%22%2C%22lastName%22%3A%22Ni%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Stefano%22%2C%22lastName%22%3A%22Morotti%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Tai%22%2C%22lastName%22%3A%22Le%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Karl%20J.%22%2C%22lastName%22%3A%22Clark%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jenna%22%2C%22lastName%22%3A%22Port%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Stephen%20C.%22%2C%22lastName%22%3A%22Ekker%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Hung%22%2C%22lastName%22%3A%22Cao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yuji%22%2C%22lastName%22%3A%22Zhang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jun%22%2C%22lastName%22%3A%22Wang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Eleonora%22%2C%22lastName%22%3A%22Grandi%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Zhiqiang%22%2C%22lastName%22%3A%22Li%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yongyong%22%2C%22lastName%22%3A%22Shi%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yigang%22%2C%22lastName%22%3A%22Li%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Alexey%20V.%22%2C%22lastName%22%3A%22Glukhov%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Xiaolei%22%2C%22lastName%22%3A%22Xu%22%7D%5D%2C%22abstractNote%22%3A%22Previously%20we%20showed%20the%20generation%20of%20a%20protein%20trap%20library%20made%20with%20the%20gene-break%20transposon%20%28GBT%29%20in%20zebrafish%20%28%26lt%3Bi%26gt%3BDanio%20rerio%26lt%3B%5C%2Fi%26gt%3B%29%20that%20could%20be%20used%20to%20facilitate%20novel%20functional%20genome%20annotation%20towards%20understanding%20molecular%20underpinnings%20of%20human%20diseases%20%28Ichino%20et%20al%2C%202020%29.%20Here%2C%20we%20report%20a%20significant%20application%20of%20this%20library%20for%20discovering%20essential%20genes%20for%20heart%20rhythm%20disorders%20such%20as%20sick%20sinus%20syndrome%20%28SSS%29.%20SSS%20is%20a%20group%20of%20heart%20rhythm%20disorders%20caused%20by%20malfunction%20of%20the%20sinus%20node%2C%20the%20heart%26%23039%3Bs%20primary%20pacemaker.%20Partially%20owing%20to%20its%20aging-associated%20phenotypic%20manifestation%20and%20low%20expressivity%2C%20molecular%20mechanisms%20of%20SSS%20remain%20difficult%20to%20decipher.%20From%20609%20GBT%20lines%20screened%2C%20we%20generated%20a%20collection%20of%2035%20zebrafish%20insertional%20cardiac%20%28ZIC%29%20mutants%20in%20which%20each%20mutant%20traps%20a%20gene%20with%20cardiac%20expression.%20We%20further%20employed%20electrocardiographic%20measurements%20to%20screen%20these%2035%20ZIC%20lines%20and%20identified%20three%20GBT%20mutants%20with%20SSS-like%20phenotypes.%20More%20detailed%20functional%20studies%20on%20one%20of%20the%20arrhythmogenic%20mutants%2C%20%26lt%3Bi%26gt%3BGBT411%26lt%3B%5C%2Fi%26gt%3B%2C%20in%20both%20zebrafish%20and%20mouse%20models%20unveiled%20%26lt%3Bi%26gt%3BDnajb6%26lt%3B%5C%2Fi%26gt%3B%20as%20a%20novel%20SSS%20causative%20gene%20with%20a%20unique%20expression%20pattern%20within%20the%20subpopulation%20of%20sinus%20node%20pacemaker%20cells%20that%20partially%20overlaps%20with%20the%20expression%20of%20hyperpolarization%20activated%20cyclic%20nucleotide%20gated%20channel%204%20%28HCN4%29%2C%20supporting%20heterogeneity%20of%20the%20cardiac%20pacemaker%20cells.%22%2C%22date%22%3A%22Oct%2018%202022%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.7554%5C%2FeLife.77327%22%2C%22ISSN%22%3A%222050-084X%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%22AMEMBFXC%22%2C%22QF52JASW%22%5D%2C%22dateModified%22%3A%222023-03-07T21%3A49%3A49Z%22%7D%7D%2C%7B%22key%22%3A%22IGRA2QYX%22%2C%22library%22%3A%7B%22id%22%3A4862227%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Mart%5Cu00ednez%20Traverso%20et%20al.%22%2C%22parsedDate%22%3A%222022-09-15%22%2C%22numChildren%22%3A1%7D%2C%22bib%22%3A%22%26lt%3Bdiv%20class%3D%26quot%3Bcsl-bib-body%26quot%3B%20style%3D%26quot%3Bline-height%3A%201.35%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%26quot%3B%26gt%3B%5Cn%20%20%26lt%3Bdiv%20class%3D%26quot%3Bcsl-entry%26quot%3B%26gt%3BMart%26%23xED%3Bnez%20Traverso%2C%20I.%20M.%2C%20Steimle%2C%20J.%20D.%2C%20Zhao%2C%20X.%20et%20al.%20%282022%29.%20LATS1%5C%2F2%20control%20TGFB-directed%20epithelial-to-mesenchymal%20transition%20in%20the%20murine%20dorsal%20cranial%20neuroepithelium%20through%20YAP%20regulation.%20%26lt%3Bi%26gt%3BDevelopment%26lt%3B%5C%2Fi%26gt%3B%20%26lt%3Bi%26gt%3B149%26lt%3B%5C%2Fi%26gt%3B%2C%20dev200860.%20%26lt%3Ba%20class%3D%26%23039%3Bzp-DOIURL%26%23039%3B%20href%3D%26%23039%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1242%5C%2Fdev.200860%26%23039%3B%26gt%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1242%5C%2Fdev.200860%26lt%3B%5C%2Fa%26gt%3B.%26lt%3B%5C%2Fdiv%26gt%3B%5Cn%26lt%3B%5C%2Fdiv%26gt%3B%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22LATS1%5C%2F2%20control%20TGFB-directed%20epithelial-to-mesenchymal%20transition%20in%20the%20murine%20dorsal%20cranial%20neuroepithelium%20through%20YAP%20regulation%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Idaliz%20M.%22%2C%22lastName%22%3A%22Mart%5Cu00ednez%20Traverso%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jeffrey%20D.%22%2C%22lastName%22%3A%22Steimle%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Xiaolei%22%2C%22lastName%22%3A%22Zhao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jun%22%2C%22lastName%22%3A%22Wang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22James%20F.%22%2C%22lastName%22%3A%22Martin%22%7D%5D%2C%22abstractNote%22%3A%22Hippo%20signaling%2C%20an%20evolutionarily%20conserved%20kinase%20cascade%20involved%20in%20organ%20size%20control%2C%20plays%20key%20roles%20in%20various%20tissue%20developmental%20processes%2C%20but%20its%20role%20in%20craniofacial%20development%20remains%20poorly%20understood.%20Using%20the%20transgenic%20Wnt1-Cre2%20driver%2C%20we%20inactivated%20the%20Hippo%20signaling%20components%20Lats1%20and%20Lats2%20in%20the%20cranial%20neuroepithelium%20of%20mouse%20embryos%20and%20found%20that%20the%20double%20conditional%20knockout%20%28DCKO%29%20of%20Lats1%5C%2F2%20resulted%20in%20neural%20tube%20and%20craniofacial%20defects.%20Lats1%5C%2F2%20DCKO%20mutant%20embryos%20had%20microcephaly%20with%20delayed%20and%20defective%20neural%20tube%20closure.%20Furthermore%2C%20neuroepithelial%20cell%20shape%20and%20architecture%20were%20disrupted%20within%20the%20cranial%20neural%20tube%20in%20Lats1%5C%2F2%20DCKO%20mutants.%20RNA%20sequencing%20of%20embryonic%20neural%20tubes%20revealed%20increased%20TGFB%20signaling%20in%20Lats1%5C%2F2%20DCKO%20mutants.%20Moreover%2C%20markers%20of%20epithelial-to-mesenchymal%20transition%20%28EMT%29%20were%20upregulated%20in%20the%20cranial%20neural%20tube.%20Inactivation%20of%20Hippo%20signaling%20downstream%20effectors%2C%20Yap%20and%20Taz%2C%20suppressed%20neuroepithelial%20defects%2C%20aberrant%20EMT%20and%20TGFB%20upregulation%20in%20Lats1%5C%2F2%20DCKO%20embryos%2C%20indicating%20that%20LATS1%5C%2F2%20function%20via%20YAP%20and%20TAZ.%20Our%20findings%20reveal%20important%20roles%20for%20Hippo%20signaling%20in%20modulating%20TGFB%20signaling%20during%20neural%20crest%20EMT.%22%2C%22date%22%3A%22Sept%2015%202022%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.1242%5C%2Fdev.200860%22%2C%22ISSN%22%3A%221477-9129%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%227IGCL8QC%22%2C%22AMEMBFXC%22%2C%22C27MTI39%22%5D%2C%22dateModified%22%3A%222023-03-07T21%3A49%3A46Z%22%7D%7D%2C%7B%22key%22%3A%222IUR7VCL%22%2C%22library%22%3A%7B%22id%22%3A4862227%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Hill%20et%20al.%22%2C%22parsedDate%22%3A%222022-06-22%22%2C%22numChildren%22%3A1%7D%2C%22bib%22%3A%22%26lt%3Bdiv%20class%3D%26quot%3Bcsl-bib-body%26quot%3B%20style%3D%26quot%3Bline-height%3A%201.35%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%26quot%3B%26gt%3B%5Cn%20%20%26lt%3Bdiv%20class%3D%26quot%3Bcsl-entry%26quot%3B%26gt%3BHill%2C%20M.%20C.%2C%20Kadow%2C%20Z.%20A.%2C%20Long%2C%20H.%20et%20al.%20%282022%29.%20Integrated%20multi-omic%20characterization%20of%20congenital%20heart%20disease.%20%26lt%3Bi%26gt%3BNature%26lt%3B%5C%2Fi%26gt%3B.%20%26lt%3Ba%20class%3D%26%23039%3Bzp-DOIURL%26%23039%3B%20href%3D%26%23039%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs41586-022-04989-3%26%23039%3B%26gt%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs41586-022-04989-3%26lt%3B%5C%2Fa%26gt%3B.%26lt%3B%5C%2Fdiv%26gt%3B%5Cn%26lt%3B%5C%2Fdiv%26gt%3B%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Integrated%20multi-omic%20characterization%20of%20congenital%20heart%20disease%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Matthew%20C.%22%2C%22lastName%22%3A%22Hill%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Zachary%20A.%22%2C%22lastName%22%3A%22Kadow%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Hali%22%2C%22lastName%22%3A%22Long%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yuka%22%2C%22lastName%22%3A%22Morikawa%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Thomas%20J.%22%2C%22lastName%22%3A%22Martin%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Emma%20J.%22%2C%22lastName%22%3A%22Birks%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Kenneth%20S.%22%2C%22lastName%22%3A%22Campbell%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jeanne%22%2C%22lastName%22%3A%22Nerbonne%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Kory%22%2C%22lastName%22%3A%22Lavine%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Lalita%22%2C%22lastName%22%3A%22Wadhwa%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jun%22%2C%22lastName%22%3A%22Wang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Diwakar%22%2C%22lastName%22%3A%22Turaga%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Iki%22%2C%22lastName%22%3A%22Adachi%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22James%20F.%22%2C%22lastName%22%3A%22Martin%22%7D%5D%2C%22abstractNote%22%3A%22The%20heart%2C%20the%20first%20organ%20to%20develop%20in%20the%20embryo%2C%20undergoes%20complex%20morphogenesis%20that%20when%20defective%20results%20in%20congenital%20heart%20disease%20%28CHD%29.%20With%20current%20therapies%2C%20more%20than%2090%25%20of%20patients%20with%20CHD%20survive%20into%20adulthood%2C%20but%20many%20suffer%20premature%20death%20from%20heart%20failure%20and%20non-cardiac%20causes1.%20Here%2C%20to%20gain%20insight%20into%20this%20disease%20progression%2C%20we%20performed%20single-nucleus%20RNA%20sequencing%20on%20157%2C273%20nuclei%20from%20control%20hearts%20and%20hearts%20from%20patients%20with%20CHD%2C%20including%20those%20with%20hypoplastic%20left%20heart%20syndrome%20%28HLHS%29%20and%20tetralogy%20of%20Fallot%2C%20two%20common%20forms%20of%20cyanotic%20CHD%20lesions%2C%20as%20well%20as%20dilated%20and%20hypertrophic%20cardiomyopathies.%20We%20observed%20CHD-specific%20cell%20states%20in%20cardiomyocytes%2C%20which%20showed%20evidence%20of%20insulin%20resistance%20and%20increased%20expression%20of%20genes%20associated%20with%20FOXO%20signalling%20and%20CRIM1.%20Cardiac%20fibroblasts%20in%20HLHS%20were%20enriched%20in%20a%20low-Hippo%20and%20high-YAP%20cell%20state%20characteristic%20of%20activated%20cardiac%20fibroblasts.%20Imaging%20mass%20cytometry%20uncovered%20a%20spatially%20resolved%20perivascular%20microenvironment%20consistent%20with%20an%20immunodeficient%20state%20in%20CHD.%20Peripheral%20immune%20cell%20profiling%20suggested%20deficient%20monocytic%20immunity%20in%20CHD%2C%20in%20agreement%20with%20the%20predilection%20in%20CHD%20to%20infection%20and%20cancer2.%20Our%20comprehensive%20phenotyping%20of%20CHD%20provides%20a%20roadmap%20towards%20future%20personalized%20treatments%20for%20CHD.%22%2C%22date%22%3A%22June%2022%202022%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.1038%5C%2Fs41586-022-04989-3%22%2C%22ISSN%22%3A%221476-4687%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%227IGCL8QC%22%2C%22SS2CP8WX%22%2C%22AMEMBFXC%22%2C%222RCWVZ4F%22%5D%2C%22dateModified%22%3A%222023-03-07T21%3A49%3A47Z%22%7D%7D%2C%7B%22key%22%3A%22Y922P4EY%22%2C%22library%22%3A%7B%22id%22%3A4862227%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Tang%20et%20al.%22%2C%22parsedDate%22%3A%222022-05-25%22%2C%22numChildren%22%3A2%7D%2C%22bib%22%3A%22%26lt%3Bdiv%20class%3D%26quot%3Bcsl-bib-body%26quot%3B%20style%3D%26quot%3Bline-height%3A%201.35%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%26quot%3B%26gt%3B%5Cn%20%20%26lt%3Bdiv%20class%3D%26quot%3Bcsl-entry%26quot%3B%26gt%3BTang%2C%20L.%2C%20Zhong%2C%20Z.%2C%20Lin%2C%20Y.%20et%20al.%20%282022%29.%20EPIXplorer%3A%20A%20web%20server%20for%20prediction%2C%20analysis%20and%20visualization%20of%20enhancer-promoter%20interactions.%20%26lt%3Bi%26gt%3BNucleic%20Acids%20Res%26lt%3B%5C%2Fi%26gt%3B%2C%20gkac397.%20%26lt%3Ba%20class%3D%26%23039%3Bzp-DOIURL%26%23039%3B%20href%3D%26%23039%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1093%5C%2Fnar%5C%2Fgkac397%26%23039%3B%26gt%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1093%5C%2Fnar%5C%2Fgkac397%26lt%3B%5C%2Fa%26gt%3B.%26lt%3B%5C%2Fdiv%26gt%3B%5Cn%26lt%3B%5C%2Fdiv%26gt%3B%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22EPIXplorer%3A%20A%20web%20server%20for%20prediction%2C%20analysis%20and%20visualization%20of%20enhancer-promoter%20interactions%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Li%22%2C%22lastName%22%3A%22Tang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Zhizhou%22%2C%22lastName%22%3A%22Zhong%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yisheng%22%2C%22lastName%22%3A%22Lin%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yifei%22%2C%22lastName%22%3A%22Yang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jun%22%2C%22lastName%22%3A%22Wang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22James%20F.%22%2C%22lastName%22%3A%22Martin%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Min%22%2C%22lastName%22%3A%22Li%22%7D%5D%2C%22abstractNote%22%3A%22Long%20distance%20enhancers%20can%20physically%20interact%20with%20promoters%20to%20regulate%20gene%20expression%20through%20formation%20of%20enhancer-promoter%20%28E-P%29%20interactions.%20Identification%20of%20E-P%20interactions%20is%20also%20important%20for%20profound%20understanding%20of%20normal%20developmental%20and%20disease-associated%20risk%20variants.%20Although%20the%20state-of-art%20predictive%20computation%20methods%20facilitate%20the%20identification%20of%20E-P%20interactions%20to%20a%20certain%20extent%2C%20currently%20there%20is%20no%20efficient%20method%20that%20can%20meet%20various%20requirements%20of%20usage.%20Here%20we%20developed%20EPIXplorer%2C%20a%20user-friendly%20web%20server%20for%20efficient%20prediction%2C%20analysis%20and%20visualization%20of%20E-P%20interactions.%20EPIXplorer%20integrates%209%20robust%20predictive%20algorithms%2C%20supports%20multiple%20types%20of%203D%20contact%20data%20and%20multi-omics%20data%20as%20input.%20The%20output%20from%20EPIXplorer%20is%20scored%2C%20fully%20annotated%20by%20regulatory%20elements%20and%20risk%20single-nucleotide%20polymorphisms%20%28SNPs%29.%20In%20addition%2C%20the%20Visualization%20and%20Downstream%20module%20provide%20further%20functional%20analysis%2C%20all%20the%20output%20files%20and%20high-quality%20images%20are%20available%20for%20download.%20Together%2C%20EPIXplorer%20provides%20a%20user-friendly%20interface%20to%20predict%20the%20E-P%20interactions%20in%20an%20acceptable%20time%2C%20as%20well%20as%20understand%20how%20the%20genome-wide%20association%20study%20%28GWAS%29%20variants%20influence%20disease%20pathology%20by%20altering%20DNA%20looping%20between%20enhancers%20and%20the%20target%20gene%20promoters.%20EPIXplorer%20is%20available%20at%20https%3A%5C%2F%5C%2Fwww.csuligroup.com%5C%2FEPIXplorer.%22%2C%22date%22%3A%22May%2025%202022%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.1093%5C%2Fnar%5C%2Fgkac397%22%2C%22ISSN%22%3A%221362-4962%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%227IGCL8QC%22%2C%22AMEMBFXC%22%2C%22ZSY78DJL%22%5D%2C%22dateModified%22%3A%222023-03-07T21%3A49%3A43Z%22%7D%7D%5D%7D
Zheng, M., Erhardt, S., Cao, Y. et al. (2023). Emerging signaling regulation of sinoatrial node dysfunction. Curr Cardiol Rep 25, 621–630. https://doi.org/10.1007/s11886-023-01885-8.
Liao, Y., Xiang, Y., Zheng, M. et al. (2023). DeepMiceTL: a deep transfer learning based prediction of mice cardiac conduction diseases using early electrocardiograms. Brief Bioinform 24, bbad109. https://doi.org/10.1093/bib/bbad109.
Zhong, Y., Tang, K., Nattel, S. et al. (2023). Myosin light-chain 4 gene-transfer attenuates atrial fibrosis while correcting autophagic flux dysregulation. Redox Biol 60, 102606. https://doi.org/10.1016/j.redox.2023.102606.
Erhardt, S. and Wang, J. (2022). Cardiac Neural Crest and Cardiac Regeneration. Cells 12, 111. https://doi.org/10.3390/cells12010111.
Zheng, M., Li, R. G., Song, J. et al. (2022). Hippo-Yap signaling maintains sinoatrial node homeostasis. Circulation 146, 1694–1711. https://doi.org/10.1161/CIRCULATIONAHA.121.058777.
Zhao, X., Tang, L., Le, T. P. et al. (2022). Yap and Taz promote osteogenesis and prevent chondrogenesis in neural crest cells in vitro and in vivo. Sci Signal 15, eabn9009. https://doi.org/10.1126/scisignal.abn9009.
Ding, Y., Lang, D., Yan, J. et al. (2022). A phenotype-based forward genetic screen identifies Dnajb6 as a sick sinus syndrome gene. Elife 11, e77327. https://doi.org/10.7554/eLife.77327.
Martínez Traverso, I. M., Steimle, J. D., Zhao, X. et al. (2022). LATS1/2 control TGFB-directed epithelial-to-mesenchymal transition in the murine dorsal cranial neuroepithelium through YAP regulation. Development 149, dev200860. https://doi.org/10.1242/dev.200860.
Hill, M. C., Kadow, Z. A., Long, H. et al. (2022). Integrated multi-omic characterization of congenital heart disease. Nature. https://doi.org/10.1038/s41586-022-04989-3.
Tang, L., Zhong, Z., Lin, Y. et al. (2022). EPIXplorer: A web server for prediction, analysis and visualization of enhancer-promoter interactions. Nucleic Acids Res, gkac397. https://doi.org/10.1093/nar/gkac397.