Xiao Li, PhD

Precise regulation of gene expression programs underlies homeostasis of various types of cardiac and immune cells in the human heart. Disruption of such intricate programs often imbalances the fibrotic and immune microenvironment in heart failure. My lab utilizes cutting-edge technologies including single-cell genomics and genome editing to explore novel mechanisms that control these programs. By understanding the diverse genomic and cellular responses to heart injury in individual patients, we aim to improve the prevention of heart failure and develop personalized treatments to enhance recovery.

See Publications

Texas Heart Institute Positions

Current Projects

  • Integration of large-scale single-cell transcriptomics and genomics data
  • Immune microenvironment that regulates cardiac function and the pathology of heart failure
  • Application of computational genomics and machine learning and in cardiac biology
  • Chromatin-associated RNA and chromatin organization in the heart

Interests

  • Cardiovascular biology
  • Molecular immunology
  • Functional genomics
  • Computational biology
  • Pediatric cardiomyopathy and graft dysfunction

Education

  • Undergraduate:

    East China Normal University (Shanghai, China)

  • Graduate:

    University of Iowa (Iowa City, IA)

  • Postgraduate:

    Postdoctoral training, University of California, San Diego (La Jolla CA)

Publications

4862227 8MLNCUY9 1 alternatives-to-animal-experimentation 10 date desc Li X 33650 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%22AV3WCVND%22%2C%22library%22%3A%7B%22id%22%3A4862227%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Zhu%20et%20al.%22%2C%22parsedDate%22%3A%222023-03-14%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%3BZhu%2C%20R.%2C%20Liu%2C%20X.%2C%20Li%2C%20X.%20et%20al.%20%282023%29.%20Response%20to%20identifying%20the%20epidermal%20dendritic%20cell%20landscape.%20%26lt%3Bi%26gt%3BImmunity%26lt%3B%5C%2Fi%26gt%3B%20%26lt%3Bi%26gt%3B56%26lt%3B%5C%2Fi%26gt%3B%2C%20461%26%23x2013%3B462.%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.immuni.2023.02.006%26%23039%3B%26gt%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1016%5C%2Fj.immuni.2023.02.006%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%22Response%20to%20identifying%20the%20epidermal%20dendritic%20cell%20landscape%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ronghui%22%2C%22lastName%22%3A%22Zhu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Xiaochun%22%2C%22lastName%22%3A%22Liu%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%22Xu%22%2C%22lastName%22%3A%22Yao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Wei%22%2C%22lastName%22%3A%22Li%22%7D%5D%2C%22abstractNote%22%3A%22%22%2C%22date%22%3A%222023-03-14%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.1016%5C%2Fj.immuni.2023.02.006%22%2C%22ISSN%22%3A%221097-4180%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%228MLNCUY9%22%2C%225WVJH2TN%22%5D%2C%22dateModified%22%3A%222023-06-08T13%3A53%3A37Z%22%7D%7D%2C%7B%22key%22%3A%22968L43DV%22%2C%22library%22%3A%7B%22id%22%3A4862227%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Eliason%20et%20al.%22%2C%22parsedDate%22%3A%222022-07-21%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%3BEliason%2C%20S.%2C%20Su%2C%20D.%2C%20Pinho%2C%20F.%20et%20al.%20%282022%29.%20HMGN2%20represses%20gene%20transcription%20via%20interaction%20with%20transcription%20factors%20Lef-1%20and%20Pitx2%20during%20amelogenesis.%20%26lt%3Bi%26gt%3BJ%20Biol%20Chem%26lt%3B%5C%2Fi%26gt%3B%20%26lt%3Bi%26gt%3B298%26lt%3B%5C%2Fi%26gt%3B%2C%20102295.%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.jbc.2022.102295%26%23039%3B%26gt%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1016%5C%2Fj.jbc.2022.102295%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%22HMGN2%20represses%20gene%20transcription%20via%20interaction%20with%20transcription%20factors%20Lef-1%20and%20Pitx2%20during%20amelogenesis%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Steven%22%2C%22lastName%22%3A%22Eliason%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Dan%22%2C%22lastName%22%3A%22Su%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Flavia%22%2C%22lastName%22%3A%22Pinho%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Zhao%22%2C%22lastName%22%3A%22Sun%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Zichao%22%2C%22lastName%22%3A%22Zhang%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%22Mason%22%2C%22lastName%22%3A%22Sweat%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Shankar%20R.%22%2C%22lastName%22%3A%22Venugopalan%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Bing%22%2C%22lastName%22%3A%22He%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Michael%22%2C%22lastName%22%3A%22Bustin%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Brad%20A.%22%2C%22lastName%22%3A%22Amendt%22%7D%5D%2C%22abstractNote%22%3A%22The%20chromatin-associated%20high%20mobility%20group%20protein%20N2%20%28HMGN2%29%20cofactor%20regulates%20transcription%20factor%20activity%20through%20both%20chromatin%20and%20protein%20interactions.%20Hmgn2%20expression%20is%20known%20to%20be%20developmentally%20regulated%2C%20but%20the%20post-transcriptional%20mechanisms%20that%20regulate%20Hmgn2%20expression%20and%20its%20precise%20roles%20in%20tooth%20development%20remain%20unclear.%20Here%2C%20we%20demonstrate%20that%20HMGN2%20inhibits%20the%20activity%20of%20multiple%20transcription%20factors%20as%20a%20general%20mechanism%20to%20regulate%20early%20development.%20Bimolecular%20fluorescence%20complementation%2C%20pull-down%2C%20and%20coimmunoprecipitation%20assays%20show%20that%20HMGN2%20interacts%20with%20the%20transcription%20factor%20Lef-1%20through%20its%20HMG-box%20domain%20as%20well%20as%20with%20other%20early%20development%20transcription%20factors%2C%20Dlx2%2C%20FoxJ1%2C%20and%20Pitx2.%20Furthermore%2C%20EMSAs%20demonstrate%20that%20HMGN2%20binding%20to%20Lef-1%20inhibits%20its%20DNA-binding%20activity.%20We%20found%20that%20Pitx2%20and%20Hmgn2%20associate%20with%20H4K5ac%20and%20H3K4me2%20chromatin%20marks%20in%20the%20proximal%20Dlx2%20promoter%2C%20demonstrating%20Hmgn2%20association%20with%20open%20chromatin.%20In%20addition%2C%20we%20demonstrate%20that%20microRNAs%20%28miRs%29%20mir-23a%20and%20miR-23b%20directly%20target%20Hmgn2%2C%20promoting%20transcriptional%20activation%20at%20several%20gene%20promoters%2C%20including%20the%20amelogenin%20promoter.%20In%5Cu00a0vivo%2C%20we%20found%20that%20decreased%20Hmgn2%20expression%20correlates%20with%20increased%20miR-23%20expression%20in%20craniofacial%20tissues%20as%20the%20murine%20embryo%20develops.%20Finally%2C%20we%20show%20that%20ablation%20of%20Hmgn2%20in%20mice%20results%20in%20increased%20amelogenin%20expression%20because%20of%20increased%20Pitx2%2C%20Dlx2%2C%20Lef-1%2C%20and%20FoxJ1%20transcriptional%20activity.%20Taken%20together%2C%20our%20results%20demonstrate%20both%20post-transcriptional%20regulation%20of%20Hmgn2%20by%20miR-23a%5C%2Fb%20and%20post-translational%20regulation%20of%20gene%20expression%20by%20Hmgn2-transcription%20factor%20interactions.%20We%20conclude%20that%20HMGN2%20regulates%20tooth%20development%20through%20its%20interaction%20with%20multiple%20transcription%20factors.%22%2C%22date%22%3A%22Jul%2021%202022%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.1016%5C%2Fj.jbc.2022.102295%22%2C%22ISSN%22%3A%221083-351X%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%228MLNCUY9%22%2C%22VTWWYEIB%22%5D%2C%22dateModified%22%3A%222022-09-02T20%3A12%3A54Z%22%7D%7D%2C%7B%22key%22%3A%22CEZMPXKR%22%2C%22library%22%3A%7B%22id%22%3A4862227%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Liu%20et%20al.%22%2C%22parsedDate%22%3A%222021-10-12%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%3BLiu%2C%20X.%2C%20Zhu%2C%20R.%2C%20Luo%2C%20Y.%20et%20al.%20%282021%29.%20Distinct%20human%20Langerhans%20cell%20subsets%20orchestrate%20reciprocal%20functions%20and%20require%20different%20developmental%20regulation.%20%26lt%3Bi%26gt%3BImmunity%26lt%3B%5C%2Fi%26gt%3B%20%26lt%3Bi%26gt%3B54%26lt%3B%5C%2Fi%26gt%3B%2C%202305-2320.e11.%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.immuni.2021.08.012%26%23039%3B%26gt%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1016%5C%2Fj.immuni.2021.08.012%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%22Distinct%20human%20Langerhans%20cell%20subsets%20orchestrate%20reciprocal%20functions%20and%20require%20different%20developmental%20regulation%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Xiaochun%22%2C%22lastName%22%3A%22Liu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ronghui%22%2C%22lastName%22%3A%22Zhu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yang%22%2C%22lastName%22%3A%22Luo%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Shangshang%22%2C%22lastName%22%3A%22Wang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yi%22%2C%22lastName%22%3A%22Zhao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Zhuoqiong%22%2C%22lastName%22%3A%22Qiu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yu%22%2C%22lastName%22%3A%22Zhang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Xiao%22%2C%22lastName%22%3A%22Liu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Xu%22%2C%22lastName%22%3A%22Yao%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%22Wei%22%2C%22lastName%22%3A%22Li%22%7D%5D%2C%22abstractNote%22%3A%22Langerhans%20cells%20%28LCs%29%20play%20a%20pivotal%20role%20in%20skin%20homeostasis%2C%20and%20the%20heterogeneity%20of%20LCs%20has%20long%20been%20considered.%20In%20this%20study%2C%20we%20have%20identified%20two%20steady-state%20%28LC1%20and%20LC2%29%20and%20two%20activated%20LC%20subsets%20in%20the%20epidermis%20of%20human%20skin%20and%20in%20LCs%20derived%20from%20CD34%2B%20hemopoietic%20stem%20cells%20%28HSC-LCs%29%20by%20utilizing%20single-cell%20RNA%20sequencing%20and%20mass%20cytometry.%20Analysis%20of%20HSC-LCs%20at%20multiple%20time-points%20during%20differentiation%20revealed%20that%20EGR1%20and%20Notch%20signaling%20were%20among%20the%20top%20pathways%20regulating%20the%20bifurcation%20of%20LC1%20and%20LC2.%20LC1%20were%20characterized%20as%20classical%20LCs%2C%20mainly%20related%20to%20innate%20immunity%20and%20antigen%20processing.%20LC2%20were%20similar%20to%20monocytes%20or%20myeloid%20dendritic%20cells%2C%20involving%20in%20immune%20responses%20and%20leukocyte%20activation.%20LC1%20remained%20stable%20under%20inflammatory%20microenvironment%2C%20whereas%20LC2%20were%20prone%20to%20being%20activated%20and%20demonstrated%20elevated%20expression%20of%20immuno-suppressive%20molecules.%20We%20revealed%20distinct%20human%20LC%20subsets%20that%20require%20different%20developmental%20regulation%20and%20orchestrate%20reciprocal%20functions.%22%2C%22date%22%3A%22Oct%2012%202021%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.1016%5C%2Fj.immuni.2021.08.012%22%2C%22ISSN%22%3A%221097-4180%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%228MLNCUY9%22%5D%2C%22dateModified%22%3A%222021-10-29T18%3A55%3A56Z%22%7D%7D%2C%7B%22key%22%3A%22PG2YT5RH%22%2C%22library%22%3A%7B%22id%22%3A4862227%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Hao%20et%20al.%22%2C%22parsedDate%22%3A%222020-11%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%3BHao%2C%20Y.%2C%20Wang%2C%20D.%2C%20Wu%2C%20S.%20et%20al.%20%282020%29.%20Active%20retrotransposons%20help%20maintain%20pericentromeric%20heterochromatin%20required%20for%20faithful%20cell%20division.%20%26lt%3Bi%26gt%3BGenome%20Res%26lt%3B%5C%2Fi%26gt%3B%20%26lt%3Bi%26gt%3B30%26lt%3B%5C%2Fi%26gt%3B%2C%201570%26%23x2013%3B1582.%20%26lt%3Ba%20class%3D%26%23039%3Bzp-DOIURL%26%23039%3B%20href%3D%26%23039%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1101%5C%2Fgr.256131.119%26%23039%3B%26gt%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1101%5C%2Fgr.256131.119%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%22Active%20retrotransposons%20help%20maintain%20pericentromeric%20heterochromatin%20required%20for%20faithful%20cell%20division%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yajing%22%2C%22lastName%22%3A%22Hao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Dongpeng%22%2C%22lastName%22%3A%22Wang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Shuheng%22%2C%22lastName%22%3A%22Wu%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%22Changwei%22%2C%22lastName%22%3A%22Shao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Peng%22%2C%22lastName%22%3A%22Zhang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jia-Yu%22%2C%22lastName%22%3A%22Chen%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Do-Hwan%22%2C%22lastName%22%3A%22Lim%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Xiang-Dong%22%2C%22lastName%22%3A%22Fu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Runsheng%22%2C%22lastName%22%3A%22Chen%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Shunmin%22%2C%22lastName%22%3A%22He%22%7D%5D%2C%22abstractNote%22%3A%22Retrotransposons%20are%20populated%20in%20vertebrate%20genomes%2C%20and%20when%20active%2C%20are%20thought%20to%20cause%20genome%20instability%20with%20potential%20benefit%20to%20genome%20evolution.%20Retrotransposon-derived%20RNAs%20are%20also%20known%20to%20give%20rise%20to%20small%20endo-siRNAs%20to%20help%20maintain%20heterochromatin%20at%20their%20sites%20of%20transcription%3B%20however%2C%20as%20not%20all%20heterochromatic%20regions%20are%20equally%20active%20in%20transcription%2C%20it%20remains%20unclear%20how%20heterochromatin%20is%20maintained%20across%20the%20genome.%20Here%2C%20we%20address%20these%20problems%20by%20defining%20the%20origins%20of%20repeat-derived%20RNAs%20and%20their%20specific%20chromatin%20locations%20in%20Drosophila%20S2%20cells.%20We%20demonstrate%20that%20repeat%20RNAs%20are%20predominantly%20derived%20from%20active%20gypsy%20elements%20and%20processed%20by%20Dcr-2%20into%20small%20RNAs%20to%20help%20maintain%20pericentromeric%20heterochromatin.%20We%20also%20show%20in%20cultured%20S2%20cells%20that%20synthetic%20repeat-derived%20endo-siRNA%20mimics%20are%20sufficient%20to%20rescue%20Dcr-2-deficiency-induced%20defects%20in%20heterochromatin%20formation%20in%20interphase%20and%20chromosome%20segregation%20during%20mitosis%2C%20demonstrating%20that%20active%20retrotransposons%20are%20required%20for%20stable%20genetic%20inheritance.%22%2C%22date%22%3A%22NOV%202020%22%2C%22language%22%3A%22English%22%2C%22DOI%22%3A%2210.1101%5C%2Fgr.256131.119%22%2C%22ISSN%22%3A%221088-9051%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fgateway.webofknowledge.com%5C%2Fgateway%5C%2FGateway.cgi%3FGWVersion%3D2%26SrcAuth%3DDynamicDOIArticle%26SrcApp%3DWOS%26KeyAID%3D10.1101%252Fgr.256131.119%26DestApp%3DDOI%26SrcAppSID%3D5DFgnSJjkTEvMJzJVmN%26SrcJTitle%3DGENOME%2BRESEARCH%26DestDOIRegistrantName%3DCold%2BSpring%2BHarbor%2BLaboratory%22%2C%22collections%22%3A%5B%228MLNCUY9%22%5D%2C%22dateModified%22%3A%222022-04-26T13%3A32%3A06Z%22%7D%7D%2C%7B%22key%22%3A%22R3N877C7%22%2C%22library%22%3A%7B%22id%22%3A4862227%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Li%20and%20Fu%22%2C%22parsedDate%22%3A%222019-09%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%3BLi%2C%20X.%20and%20Fu%2C%20X.-D.%20%282019%29.%20Chromatin-associated%20RNAs%20as%20facilitators%20of%20functional%20genomic%20interactions.%20%26lt%3Bi%26gt%3BNat%20Rev%20Genet%26lt%3B%5C%2Fi%26gt%3B%20%26lt%3Bi%26gt%3B20%26lt%3B%5C%2Fi%26gt%3B%2C%20503%26%23x2013%3B519.%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%2Fs41576-019-0135-1%26%23039%3B%26gt%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs41576-019-0135-1%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%22Chromatin-associated%20RNAs%20as%20facilitators%20of%20functional%20genomic%20interactions%22%2C%22creators%22%3A%5B%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%22Xiang-Dong%22%2C%22lastName%22%3A%22Fu%22%7D%5D%2C%22abstractNote%22%3A%22Mammalian%20genomes%20are%20extensively%20transcribed%2C%20which%20produces%20a%20large%20number%20of%20both%20coding%20and%20non-coding%20transcripts.%20Various%20RNAs%20are%20physically%20associated%20with%20chromatin%2C%20through%20being%20either%20retained%20in%20cis%20at%20their%20site%20of%20transcription%20or%20recruited%20in%20trans%20to%20other%20genomic%20regions.%20Driven%20by%20recent%20technological%20innovations%20for%20detecting%20chromatin-associated%20RNAs%2C%20diverse%20roles%20are%20being%20revealed%20for%20these%20RNAs%20and%20associated%20RNA-binding%20proteins%20%28RBPs%29%20in%20gene%20regulation%20and%20genome%20function.%20Such%20functions%20include%20locus-specific%20roles%20in%20gene%20activation%20and%20silencing%2C%20as%20well%20as%20emerging%20roles%20in%20higher-order%20genome%20organization%2C%20such%20as%20involvement%20in%20long-range%20enhancer-promoter%20interactions%2C%20transcription%20hubs%2C%20heterochromatin%2C%20nuclear%20bodies%20and%20phase%20transitions.%22%2C%22date%22%3A%222019-09%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.1038%5C%2Fs41576-019-0135-1%22%2C%22ISSN%22%3A%221471-0064%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%228MLNCUY9%22%5D%2C%22dateModified%22%3A%222022-04-18T15%3A22%3A15Z%22%7D%7D%2C%7B%22key%22%3A%22SD4WSWHZ%22%2C%22library%22%3A%7B%22id%22%3A4862227%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Zhou%20et%20al.%22%2C%22parsedDate%22%3A%222019-07%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%3BZhou%2C%20B.%2C%20Li%2C%20X.%2C%20Luo%2C%20D.%20et%20al.%20%282019%29.%20GRID-seq%20for%20comprehensive%20analysis%20of%20global%20RNA-chromatin%20interactions.%20%26lt%3Bi%26gt%3BNat%20Protoc%26lt%3B%5C%2Fi%26gt%3B%20%26lt%3Bi%26gt%3B14%26lt%3B%5C%2Fi%26gt%3B%2C%202036%26%23x2013%3B2068.%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%2Fs41596-019-0172-4%26%23039%3B%26gt%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs41596-019-0172-4%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%22GRID-seq%20for%20comprehensive%20analysis%20of%20global%20RNA-chromatin%20interactions%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Bing%22%2C%22lastName%22%3A%22Zhou%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%22Daji%22%2C%22lastName%22%3A%22Luo%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Do-Hwan%22%2C%22lastName%22%3A%22Lim%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yu%22%2C%22lastName%22%3A%22Zhou%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Xiang-Dong%22%2C%22lastName%22%3A%22Fu%22%7D%5D%2C%22abstractNote%22%3A%22Chromatin%20in%20higher%20eukaryotic%20nuclei%20is%20extensively%20bound%20by%20various%20RNA%20species.%20We%20recently%20developed%20a%20method%20for%20in%20situ%20capture%20of%20global%20RNA%20interactions%20with%20DNA%20by%20deep%20sequencing%20%28GRID-seq%29%20of%20fixed%20permeabilized%20nuclei%20that%20allows%20identification%20of%20the%20entire%20repertoire%20of%20chromatin-associated%20RNAs%20in%20an%20unbiased%20manner.%20The%20experimental%20design%20of%20GRID-seq%20is%20related%20to%20those%20of%20two%20recently%20published%20strategies%20%28MARGI%20%28mapping%20RNA-genome%20interactions%29%20and%20ChAR-seq%20%28chromatin-associated%20RNA%20sequencing%29%29%2C%20which%20also%20use%20a%20bivalent%20linker%20to%20ligate%20RNA%20and%20DNA%20in%20proximity.%20Importantly%2C%20however%2C%20GRID-seq%20also%20implements%20a%20combined%20experimental%20and%20computational%20approach%20to%20control%20nonspecific%20RNA-DNA%20interactions%20that%20are%20likely%20to%20occur%20during%20library%20construction%2C%20which%20is%20critical%20for%20accurate%20interpretation%20of%20detected%20RNA-DNA%20interactions.%20GRID-seq%20typically%20finds%20both%20coding%20and%20non-coding%20RNAs%20%28ncRNAs%29%20that%20interact%20with%20tissue-specific%20promoters%20and%20enhancers%2C%20especially%20super-enhancers%2C%20from%20which%20a%20global%20promoter-enhancer%20connectivity%20map%20can%20be%20deduced.%20Here%2C%20we%20provide%20a%20detailed%20protocol%20for%20GRID-seq%20that%20includes%20nuclei%20preparation%2C%20chromatin%20fragmentation%2C%20RNA%20and%20DNA%20in%20situ%20ligation%20with%20a%20bivalent%20linker%2C%20PCR%20amplification%20and%20high-throughput%20sequencing.%20To%20further%20enhance%20the%20utility%20of%20GRID-seq%2C%20we%20include%20a%20pipeline%20for%20data%20analysis%2C%20called%20GridTools%2C%20into%20which%20key%20steps%20such%20as%20background%20correction%20and%20inference%20of%20genomic%20element%20proximity%20are%20integrated.%20For%20researchers%20experienced%20in%20molecular%20biology%20with%20minimal%20bioinformatics%20skills%2C%20the%20protocol%20typically%20takes%204-5%20d%20from%20cell%20fixation%20to%20library%20construction%20and%202-3%20d%20for%20data%20processing.%22%2C%22date%22%3A%222019-07%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.1038%5C%2Fs41596-019-0172-4%22%2C%22ISSN%22%3A%221750-2799%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%228MLNCUY9%22%5D%2C%22dateModified%22%3A%222022-04-18T15%3A22%3A15Z%22%7D%7D%2C%7B%22key%22%3A%2278Y8TUGQ%22%2C%22library%22%3A%7B%22id%22%3A4862227%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Kousa%20et%20al.%22%2C%22parsedDate%22%3A%222019-05-15%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%3BKousa%2C%20Y.%20A.%2C%20Zhu%2C%20H.%2C%20Fakhouri%2C%20W.%20D.%20et%20al.%20%282019%29.%20The%20TFAP2A-IRF6-GRHL3%20genetic%20pathway%20is%20conserved%20in%20neurulation.%20%26lt%3Bi%26gt%3BHum%20Mol%20Genet%26lt%3B%5C%2Fi%26gt%3B%20%26lt%3Bi%26gt%3B28%26lt%3B%5C%2Fi%26gt%3B%2C%201726%26%23x2013%3B1737.%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%2Fhmg%5C%2Fddz010%26%23039%3B%26gt%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1093%5C%2Fhmg%5C%2Fddz010%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%22The%20TFAP2A-IRF6-GRHL3%20genetic%20pathway%20is%20conserved%20in%20neurulation%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Youssef%20A.%22%2C%22lastName%22%3A%22Kousa%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Huiping%22%2C%22lastName%22%3A%22Zhu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Walid%20D.%22%2C%22lastName%22%3A%22Fakhouri%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yunping%22%2C%22lastName%22%3A%22Lei%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Akira%22%2C%22lastName%22%3A%22Kinoshita%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Raeuf%20R.%22%2C%22lastName%22%3A%22Roushangar%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Nicole%20K.%22%2C%22lastName%22%3A%22Patel%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22A.%20J.%22%2C%22lastName%22%3A%22Agopian%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Wei%22%2C%22lastName%22%3A%22Yang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Elizabeth%20J.%22%2C%22lastName%22%3A%22Leslie%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Tamara%20D.%22%2C%22lastName%22%3A%22Busch%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Tamer%20A.%22%2C%22lastName%22%3A%22Mansour%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%22Arianna%20L.%22%2C%22lastName%22%3A%22Smith%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Edward%20B.%22%2C%22lastName%22%3A%22Li%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Dhruv%20B.%22%2C%22lastName%22%3A%22Sharma%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Trevor%20J.%22%2C%22lastName%22%3A%22Williams%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yang%22%2C%22lastName%22%3A%22Chai%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Brad%20A.%22%2C%22lastName%22%3A%22Amendt%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Eric%20C.%22%2C%22lastName%22%3A%22Liao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Laura%20E.%22%2C%22lastName%22%3A%22Mitchell%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Alexander%20G.%22%2C%22lastName%22%3A%22Bassuk%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Simon%22%2C%22lastName%22%3A%22Gregory%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Allison%22%2C%22lastName%22%3A%22Ashley-Koch%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Gary%20M.%22%2C%22lastName%22%3A%22Shaw%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Richard%20H.%22%2C%22lastName%22%3A%22Finnell%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Brian%20C.%22%2C%22lastName%22%3A%22Schutte%22%7D%5D%2C%22abstractNote%22%3A%22Mutations%20in%20IRF6%2C%20TFAP2A%20and%20GRHL3%20cause%20orofacial%20clefting%20syndromes%20in%20humans.%20However%2C%20Tfap2a%20and%20Grhl3%20are%20also%20required%20for%20neurulation%20in%20mice.%20Here%2C%20we%20found%20that%20homeostasis%20of%20Irf6%20is%20also%20required%20for%20development%20of%20the%20neural%20tube%20and%20associated%20structures.%20Over-expression%20of%20Irf6%20caused%20exencephaly%2C%20a%20rostral%20neural%20tube%20defect%2C%20through%20suppression%20of%20Tfap2a%20and%20Grhl3%20expression.%20Conversely%2C%20loss%20of%20Irf6%20function%20caused%20a%20curly%20tail%20and%20coincided%20with%20a%20reduction%20of%20Tfap2a%20and%20Grhl3%20expression%20in%20tail%20tissues.%20To%20test%20whether%20Irf6%20function%20in%20neurulation%20was%20conserved%2C%20we%20sequenced%20samples%20obtained%20from%20human%20cases%20of%20spina%20bifida%20and%20anencephaly.%20We%20found%20two%20likely%20disease-causing%20variants%20in%20two%20samples%20from%20patients%20with%20spina%20bifida.%20Overall%2C%20these%20data%20suggest%20that%20the%20Tfap2a-Irf6-Grhl3%20genetic%20pathway%20is%20shared%20by%20two%20embryologically%20distinct%20morphogenetic%20events%20that%20previously%20were%20considered%20independent%20during%20mammalian%20development.%20In%20addition%2C%20these%20data%20suggest%20new%20candidates%20to%20delineate%20the%20genetic%20architecture%20of%20neural%20tube%20defects%20and%20new%20therapeutic%20targets%20to%20prevent%20this%20common%20birth%20defect.%22%2C%22date%22%3A%222019-05-15%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.1093%5C%2Fhmg%5C%2Fddz010%22%2C%22ISSN%22%3A%221460-2083%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%228MLNCUY9%22%5D%2C%22dateModified%22%3A%222022-04-18T15%3A22%3A15Z%22%7D%7D%2C%7B%22key%22%3A%22EKU4VIPW%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%222019-05-01%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%3BZhao%2C%20Y.%2C%20Li%2C%20X.%2C%20Zhao%2C%20W.%20et%20al.%20%282019%29.%20Single-cell%20transcriptomic%20landscape%20of%20nucleated%20cells%20in%20umbilical%20cord%20blood.%20%26lt%3Bi%26gt%3BGigascience%26lt%3B%5C%2Fi%26gt%3B%20%26lt%3Bi%26gt%3B8%26lt%3B%5C%2Fi%26gt%3B%2C%20giz047.%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%2Fgigascience%5C%2Fgiz047%26%23039%3B%26gt%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1093%5C%2Fgigascience%5C%2Fgiz047%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%22Single-cell%20transcriptomic%20landscape%20of%20nucleated%20cells%20in%20umbilical%20cord%20blood%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yi%22%2C%22lastName%22%3A%22Zhao%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%22Weihua%22%2C%22lastName%22%3A%22Zhao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jingwan%22%2C%22lastName%22%3A%22Wang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jiawei%22%2C%22lastName%22%3A%22Yu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ziyun%22%2C%22lastName%22%3A%22Wan%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Kai%22%2C%22lastName%22%3A%22Gao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Gang%22%2C%22lastName%22%3A%22Yi%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Xie%22%2C%22lastName%22%3A%22Wang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Bingbing%22%2C%22lastName%22%3A%22Fan%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Qinkai%22%2C%22lastName%22%3A%22Wu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Bangwei%22%2C%22lastName%22%3A%22Chen%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Feng%22%2C%22lastName%22%3A%22Xie%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jinghua%22%2C%22lastName%22%3A%22Wu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Wei%22%2C%22lastName%22%3A%22Zhang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Fang%22%2C%22lastName%22%3A%22Chen%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Huanming%22%2C%22lastName%22%3A%22Yang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jian%22%2C%22lastName%22%3A%22Wang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Xun%22%2C%22lastName%22%3A%22Xu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Bin%22%2C%22lastName%22%3A%22Li%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Shiping%22%2C%22lastName%22%3A%22Liu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yong%22%2C%22lastName%22%3A%22Hou%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Xiao%22%2C%22lastName%22%3A%22Liu%22%7D%5D%2C%22abstractNote%22%3A%22BACKGROUND%3A%20For%20both%20pediatric%20and%20adult%20patients%2C%20umbilical%20cord%20blood%20%28UCB%29%20transplant%20is%20a%20therapeutic%20option%20for%20a%20variety%20of%20hematologic%20diseases%2C%20such%20as%20blood%20cancers%2C%20myeloproliferative%20disorders%2C%20genetic%20diseases%2C%20and%20metabolic%20disorders.%20However%2C%20the%20level%20of%20cellular%20heterogeneity%20and%20diversity%20of%20nucleated%20cells%20in%20UCB%20has%20not%20yet%20been%20assessed%20in%20an%20unbiased%20and%20systemic%20fashion.%20In%20the%20present%20study%2C%20nucleated%20cells%20from%20UCB%20were%20subjected%20to%20single-cell%20RNA%20sequencing%20to%20simultaneously%20profile%20the%20gene%20expression%20signatures%20of%20thousands%20of%20cells%2C%20generating%20a%20rich%20resource%20for%20further%20functional%20studies.%20Here%2C%20we%20report%20the%20transcriptomes%20of%2017%2C637%20UCB%20cells%2C%20covering%2012%20major%20cell%20types%2C%20many%20of%20which%20can%20be%20further%20divided%20into%20distinct%20subpopulations.%5CnRESULTS%3A%20Pseudotemporal%20ordering%20of%20nucleated%20red%20blood%20cells%20identifies%20wave-like%20activation%20and%20suppression%20of%20transcription%20regulators%2C%20leading%20to%20a%20polarized%20cellular%20state%2C%20which%20may%20reflect%20nucleated%20red%20blood%20cell%20maturation.%20Progenitor%20cells%20in%20UCB%20also%20comprise%202%20subpopulations%20with%20activation%20of%20divergent%20transcription%20programs%2C%20leading%20to%20specific%20cell%20fate%20commitment.%20Detailed%20profiling%20of%20cytotoxic%20cell%20populations%20unveiled%20granzymes%20B%20and%20K%20signatures%20in%20natural%20killer%20and%20natural%20killer%20T-cell%20types%20in%20UCB.%5CnCONCLUSIONS%3A%20Taken%20together%2C%20our%20data%20form%20a%20comprehensive%20single-cell%20transcriptomic%20landscape%20that%20reveals%20previously%20unrecognized%20cell%20types%2C%20pathways%2C%20and%20mechanisms%20of%20gene%20expression%20regulation.%20These%20data%20may%20contribute%20to%20the%20efficacy%20and%20outcome%20of%20UCB%20transplant%2C%20broadening%20the%20scope%20of%20research%20and%20clinical%20innovations.%22%2C%22date%22%3A%222019-05-01%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.1093%5C%2Fgigascience%5C%2Fgiz047%22%2C%22ISSN%22%3A%222047-217X%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%228MLNCUY9%22%5D%2C%22dateModified%22%3A%222022-04-18T15%3A22%3A15Z%22%7D%7D%2C%7B%22key%22%3A%22YU785XTL%22%2C%22library%22%3A%7B%22id%22%3A4862227%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Wang%20et%20al.%22%2C%22parsedDate%22%3A%222018%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%3BWang%2C%20L.%2C%20Zhang%2C%20W.%2C%20Lin%2C%20L.%20et%20al.%20%282018%29.%20A%20comprehensive%20analysis%20of%20the%20T%20and%20B%20lymphocytes%20repertoire%20shaped%20by%20HIV%20vaccines.%20%26lt%3Bi%26gt%3BFront%20Immunol%26lt%3B%5C%2Fi%26gt%3B%20%26lt%3Bi%26gt%3B9%26lt%3B%5C%2Fi%26gt%3B%2C%202194.%20%26lt%3Ba%20class%3D%26%23039%3Bzp-DOIURL%26%23039%3B%20href%3D%26%23039%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.3389%5C%2Ffimmu.2018.02194%26%23039%3B%26gt%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.3389%5C%2Ffimmu.2018.02194%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%20comprehensive%20analysis%20of%20the%20T%20and%20B%20lymphocytes%20repertoire%20shaped%20by%20HIV%20vaccines%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Longlong%22%2C%22lastName%22%3A%22Wang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Wei%22%2C%22lastName%22%3A%22Zhang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Liya%22%2C%22lastName%22%3A%22Lin%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%22Nitin%20K.%22%2C%22lastName%22%3A%22Saksena%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jinghua%22%2C%22lastName%22%3A%22Wu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Shiyu%22%2C%22lastName%22%3A%22Wang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Joseph%20G.%22%2C%22lastName%22%3A%22Joyce%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Xiuqing%22%2C%22lastName%22%3A%22Zhang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Huanming%22%2C%22lastName%22%3A%22Yang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jian%22%2C%22lastName%22%3A%22Wang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22I.-Ming%22%2C%22lastName%22%3A%22Wang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Xiao%22%2C%22lastName%22%3A%22Liu%22%7D%5D%2C%22abstractNote%22%3A%22The%20exploitation%20of%20various%20human%20immunodeficiency%20virus%20type-1%20%28HIV-1%29%20vaccines%20has%20posed%20great%20challenges%20for%20the%20researchers%20in%20precisely%20evaluating%20the%20vaccine-induced%20immune%20responses%2C%20however%2C%20the%20understanding%20of%20vaccination%20response%20suffers%20from%20the%20lack%20of%20unbiased%20characterization%20of%20the%20immune%20landscape.%20The%20rapid%20development%20of%20high%20throughput%20sequencing%20%28HTS%29%20makes%20it%20possible%20to%20scrutinize%20the%20extremely%20complicated%20immunological%20responses%20during%20vaccination.%20In%20the%20current%20study%2C%20three%20vaccines%2C%20namely%20N36%2C%20N51%2C%20and%205-Helix%20based%20on%20the%20HIV-1%20gp41%20pre-hairpin%20fusion%20intermediate%20were%20applied%20in%20rhesus%20macaques.%20We%20assessed%20the%20longitudinal%20vaccine%20responses%20using%20HTS%2C%20which%20delineated%20the%20evolutionary%20features%20of%20both%20T%20cell%20and%20B%20cell%20receptor%20repertoires%20with%20extreme%20diversities.%20Upon%20vaccination%2C%20we%20unexpectedly%20found%20significant%20discrepancies%20in%20the%20landscapes%20of%20T-cell%20and%20B-cell%20repertoires%2C%20together%20with%20the%20detection%20of%20significant%20class%20switching%20and%20the%20lineage%20expansion%20of%20the%20B%20cell%20receptor%20or%20immunoglobulin%20heavy%20chain%20%28IGH%29%20repertoire.%20The%20vaccine-induced%20expansions%20of%20lineages%20were%20further%20evaluated%20for%20mutation%20rate%2C%20lineage%20abundance%2C%20and%20lineage%20size%20features%20in%20their%20IGH%20repertoires.%20Collectively%2C%20these%20findings%20conclude%20that%20the%20N51%20vaccine%20displayed%20superior%20performance%20in%20inducing%20the%20class-switch%20of%20B%20cell%20isotypes%20and%20promoting%20mutations%20of%20IgM%20B%20cells.%20In%20addition%2C%20the%20systematic%20HTS%20analysis%20of%20the%20immune%20repertoires%20demonstrates%20its%20wide%20applicability%20in%20enhancing%20the%20understanding%20of%20immunologic%20changes%20during%20pathogen%20challenge%2C%20and%20will%20guide%20the%20development%2C%20evaluation%2C%20and%20exploitation%20of%20new%20generation%20of%20diagnostic%20markers%2C%20immunotherapies%2C%20and%20vaccine%20strategies.%22%2C%22date%22%3A%222018%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.3389%5C%2Ffimmu.2018.02194%22%2C%22ISSN%22%3A%221664-3224%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%228MLNCUY9%22%5D%2C%22dateModified%22%3A%222022-04-26T13%3A23%3A53Z%22%7D%7D%2C%7B%22key%22%3A%22CS3M9DPM%22%2C%22library%22%3A%7B%22id%22%3A4862227%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Li%20et%20al.%22%2C%22parsedDate%22%3A%222017-10%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%3BLi%2C%20X.%2C%20Zhou%2C%20B.%2C%20Chen%2C%20L.%20et%20al.%20%282017%29.%20GRID-seq%20reveals%20the%20global%20RNA-chromatin%20interactome.%20%26lt%3Bi%26gt%3BNat%20Biotechnol%26lt%3B%5C%2Fi%26gt%3B%20%26lt%3Bi%26gt%3B35%26lt%3B%5C%2Fi%26gt%3B%2C%20940%26%23x2013%3B950.%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%2Fnbt.3968%26%23039%3B%26gt%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fnbt.3968%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%22GRID-seq%20reveals%20the%20global%20RNA-chromatin%20interactome%22%2C%22creators%22%3A%5B%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%22Bing%22%2C%22lastName%22%3A%22Zhou%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Liang%22%2C%22lastName%22%3A%22Chen%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Lan-Tao%22%2C%22lastName%22%3A%22Gou%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Hairi%22%2C%22lastName%22%3A%22Li%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Xiang-Dong%22%2C%22lastName%22%3A%22Fu%22%7D%5D%2C%22abstractNote%22%3A%22Higher%20eukaryotic%20genomes%20are%20bound%20by%20a%20large%20number%20of%20coding%20and%20non-coding%20RNAs%2C%20but%20approaches%20to%20comprehensively%20map%20the%20identity%20and%20binding%20sites%20of%20these%20RNAs%20are%20lacking.%20Here%20we%20report%20a%20method%20to%20capture%20in%20situ%20global%20RNA%20interactions%20with%20DNA%20by%20deep%20sequencing%20%28GRID-seq%29%2C%20which%20enables%20the%20comprehensive%20identification%20of%20the%20entire%20repertoire%20of%20chromatin-interacting%20RNAs%20and%20their%20respective%20binding%20sites.%20In%20human%2C%20mouse%2C%20and%20Drosophila%20cells%2C%20we%20detected%20a%20large%20set%20of%20tissue-specific%20coding%20and%20non-coding%20RNAs%20that%20are%20bound%20to%20active%20promoters%20and%20enhancers%2C%20especially%20super-enhancers.%20Assuming%20that%20most%20mRNA-chromatin%20interactions%20indicate%20the%20physical%20proximity%20of%20a%20promoter%20and%20an%20enhancer%2C%20we%20constructed%20a%20three-dimensional%20global%20connectivity%20map%20of%20promoters%20and%20enhancers%2C%20revealing%20transcription-activity-linked%20genomic%20interactions%20in%20the%20nucleus.%22%2C%22date%22%3A%222017-10%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.1038%5C%2Fnbt.3968%22%2C%22ISSN%22%3A%221546-1696%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%228MLNCUY9%22%5D%2C%22dateModified%22%3A%222022-04-18T15%3A22%3A15Z%22%7D%7D%5D%7D
Zhu, R., Liu, X., Li, X. et al. (2023). Response to identifying the epidermal dendritic cell landscape. Immunity 56, 461–462. https://doi.org/10.1016/j.immuni.2023.02.006.
Eliason, S., Su, D., Pinho, F. et al. (2022). HMGN2 represses gene transcription via interaction with transcription factors Lef-1 and Pitx2 during amelogenesis. J Biol Chem 298, 102295. https://doi.org/10.1016/j.jbc.2022.102295.
Liu, X., Zhu, R., Luo, Y. et al. (2021). Distinct human Langerhans cell subsets orchestrate reciprocal functions and require different developmental regulation. Immunity 54, 2305-2320.e11. https://doi.org/10.1016/j.immuni.2021.08.012.
Hao, Y., Wang, D., Wu, S. et al. (2020). Active retrotransposons help maintain pericentromeric heterochromatin required for faithful cell division. Genome Res 30, 1570–1582. https://doi.org/10.1101/gr.256131.119.
Li, X. and Fu, X.-D. (2019). Chromatin-associated RNAs as facilitators of functional genomic interactions. Nat Rev Genet 20, 503–519. https://doi.org/10.1038/s41576-019-0135-1.
Zhou, B., Li, X., Luo, D. et al. (2019). GRID-seq for comprehensive analysis of global RNA-chromatin interactions. Nat Protoc 14, 2036–2068. https://doi.org/10.1038/s41596-019-0172-4.
Kousa, Y. A., Zhu, H., Fakhouri, W. D. et al. (2019). The TFAP2A-IRF6-GRHL3 genetic pathway is conserved in neurulation. Hum Mol Genet 28, 1726–1737. https://doi.org/10.1093/hmg/ddz010.
Zhao, Y., Li, X., Zhao, W. et al. (2019). Single-cell transcriptomic landscape of nucleated cells in umbilical cord blood. Gigascience 8, giz047. https://doi.org/10.1093/gigascience/giz047.
Wang, L., Zhang, W., Lin, L. et al. (2018). A comprehensive analysis of the T and B lymphocytes repertoire shaped by HIV vaccines. Front Immunol 9, 2194. https://doi.org/10.3389/fimmu.2018.02194.
Li, X., Zhou, B., Chen, L. et al. (2017). GRID-seq reveals the global RNA-chromatin interactome. Nat Biotechnol 35, 940–950. https://doi.org/10.1038/nbt.3968.