Cardiac cell type–specific gene regulatory programs and disease risk association
Abstract: Misregulated gene expression in human hearts can result in cardiovascular diseases that are leading causes of mortality worldwide. However, the limited information on the genomic location of candidate cis-regulatory elements (cCREs) such as enhancers and promoters in distinct cardiac cell types has restricted the understanding of these diseases. Here, we defined >287,000 cCREs in the four chambers of the human heart at single-cell resolution, which revealed cCREs and candidate transcription factors associated with cardiac cell types in a region-dependent manner and during heart failure. We further found cardiovascular disease–associated genetic variants enriched within these cCREs including 38 candidate causal atrial fibrillation variants localized to cardiomyocyte cCREs. Additional functional studies revealed that two of these variants affect a cCRE controlling KCNH2/HERG expression and action potential repolarization. Overall, this atlas of human cardiac cCREs provides the foundation for illuminating cell type–specific gene regulation in human hearts during health and disease
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Anmerkungen
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ISSN: 2375-2548
- Klassifikation
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Medizin, Gesundheit
- Ereignis
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Veröffentlichung
- (wo)
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Freiburg
- (wer)
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Universität
- (wann)
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2024
- Urheber
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Hocker, James D.
Poirion, Olivier B.
Zhu, Fugui
Buchanan, Justin
Zhang, Kai
Chiou, Joshua
Wang, Tsui-Min
Zhang, Qingquan
Hou, Xiaomeng
Li, Yang E.
Zhang, Yanxiao
Farah, Elie N.
Wang, Allen
McCulloch, Andrew D.
Gaulton, Kyle J.
Ren, Bing
Chi, Neil C.
Preißl, Sebastian
- DOI
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10.1126/sciadv.abf1444
- URN
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urn:nbn:de:bsz:25-freidok-2441303
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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14.08.2025, 10:48 MESZ
Datenpartner
Deutsche Nationalbibliothek. Bei Fragen zum Objekt wenden Sie sich bitte an den Datenpartner.
Beteiligte
- Hocker, James D.
- Poirion, Olivier B.
- Zhu, Fugui
- Buchanan, Justin
- Zhang, Kai
- Chiou, Joshua
- Wang, Tsui-Min
- Zhang, Qingquan
- Hou, Xiaomeng
- Li, Yang E.
- Zhang, Yanxiao
- Farah, Elie N.
- Wang, Allen
- McCulloch, Andrew D.
- Gaulton, Kyle J.
- Ren, Bing
- Chi, Neil C.
- Preißl, Sebastian
- Universität
Entstanden
- 2024
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