Transient HES5 Activity Instructs Mesodermal Cells toward a Cardiac Fate

Ana G. Freire, Avinash Waghray, Francisca Soares-da-Silva, Tatiana P. Resende, Dung Fang Lee, Carlos Filipe Pereira, Diana S. Nascimento, Ihor R. Lemischka, Perpétua Pinto-do-Ó

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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.

Original languageEnglish
Pages (from-to)136-148
Number of pages13
JournalStem Cell Reports
Volume9
Issue number1
DOIs
StatePublished - 11 Jul 2017

Keywords

  • Hes5
  • cardiac fate specification
  • nascent mesoderm
  • notch signaling pathway

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