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Transient HES5 Activity Instructs Mesodermal Cells toward a Cardiac Fate

Freire, Ana G.; Waghray, Avinash; Soares-da-Silva, Francisca; Resende, Tatiana P.; Lee, Dung Fang; Pereira, Carlos Filipe LU ; Nascimento, Diana S.; Lemischka, Ihor R. and Pinto-do-Ó, Perpétua (2017) In Stem Cell Reports 9(1). p.136-148
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... (More)

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.

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author
publishing date
type
Contribution to journal
publication status
published
keywords
cardiac fate specification, Hes5, nascent mesoderm, notch signaling pathway
in
Stem Cell Reports
volume
9
issue
1
pages
13 pages
publisher
Cell Press
external identifiers
  • scopus:85021126795
ISSN
2213-6711
DOI
10.1016/j.stemcr.2017.05.025
language
English
LU publication?
no
id
496bc610-b8d6-4b15-8801-6d08ef05b07e
date added to LUP
2017-10-02 17:21:28
date last changed
2018-01-07 12:20:13
@article{496bc610-b8d6-4b15-8801-6d08ef05b07e,
  abstract     = {<p>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.</p>},
  author       = {Freire, Ana G. and Waghray, Avinash and Soares-da-Silva, Francisca and Resende, Tatiana P. and Lee, Dung Fang and Pereira, Carlos Filipe and Nascimento, Diana S. and Lemischka, Ihor R. and Pinto-do-Ó, Perpétua},
  issn         = {2213-6711},
  keyword      = {cardiac fate specification,Hes5,nascent mesoderm,notch signaling pathway},
  language     = {eng},
  month        = {07},
  number       = {1},
  pages        = {136--148},
  publisher    = {Cell Press},
  series       = {Stem Cell Reports},
  title        = {Transient HES5 Activity Instructs Mesodermal Cells toward a Cardiac Fate},
  url          = {http://dx.doi.org/10.1016/j.stemcr.2017.05.025},
  volume       = {9},
  year         = {2017},
}