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Title: | Transient HES5 Activity Instructs Mesodermal Cells toward a Cardiac Fate | Authors: | Freire, Ana G. Waghray, Avinash Soares-da-Silva, Francisca Resende, Tatiana P. Lee, Dung-Fang Pereira, Carlos Filipe Nascimento, Diana S. Lemischka, Ihor R. Pinto-do-Ó, Perpétua |
Keywords: | Hes5; cardiac fate specification; nascent mesoderm; notch signaling pathway | Issue Date: | 11-Jul-2017 | Publisher: | Elsevier | Project: | Research was funded by NIH (5R01GM078465) and the Empire State Stem Cell Fund through New York State Department of Health (NYSTEM: C024176) to I.R.L.; by European Structural and Investment Funds (ESIF), under Lisbon Portugal Regional Operational Programme and National Funds through Foundation for Science and Technology (FCT) under project POCI-01-0145- FEDER-016385 to P.P.-O´ . A.G.F. and T.P.R. were supported by FCT (SFRH/BD/64715/2009 and SFRH/BPD/80588/2011, respectively); D.-F.L. by NIH Pathway to Independence Award (K99CA181496); and C.-F.P. by Charles H. Revson Senior Fellowship in Biomedical Science (New York) and FCT investigator IF/00646/2015. P.P.-O´ . was recipient of an invited scientist grant by Institut Pasteur, Paris, France. | Serial title, monograph or event: | Stem Cell Reports | Volume: | 9 | Issue: | 1 | Abstract: | Notch signaling plays a role in specifying a cardiac fate but the downstream effectors remain unknown. In this study we implicate the Notch downstream effector HES5 in cardiogenesis. We show transient Hes5 expression in early mesoderm of gastrulating embryos and demonstrate, by loss and gain-of-function experiments in mouse embryonic stem cells, that HES5 favors cardiac over primitive erythroid fate. Hes5 overexpression promotes upregulation of the cardiac gene Isl1, while the hematopoietic regulator Scl is downregulated. Moreover, whereas a pulse of Hes5 instructs cardiac commitment, sustained expression after lineage specification impairs progression of differentiation to contracting cardiomyocytes. These findings establish a role for HES5 in cardiogenesis and provide insights into the early cardiac molecular network. | URI: | https://hdl.handle.net/10316/108395 | ISSN: | 22136711 | DOI: | 10.1016/j.stemcr.2017.05.025 | Rights: | openAccess |
Appears in Collections: | I&D CNC - Artigos em Revistas Internacionais FMUC Medicina - Artigos em Revistas Internacionais |
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Transient HES5 Activity Instructs Mesodermal Cells toward a Cardiac Fate.pdf | 3.32 MB | Adobe PDF | View/Open |
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