Transient HES5 Activity Instructs Mesodermal Cells Toward a Cardiac Fate

July 11, 2017 / Volume 9, Issue 1
Stem Cell Reports

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

Related Data:

ChIP-seq Data



  • Hes5 is expressed in the nascent mesoderm of gastrulating mouse embryos
  • Hes5 knockdown enhances primitive erythropoiesis in mESCs
  • A stage-specific pulse of Hes5 instructs preferential cardiac fate in mESCs
  • Sustained Hes5 activation impairs differentiation to contracting cardiomyocytes


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.