Transient HES5 Activity Instructs Mesodermal Cells toward a Cardiac Fate
(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.
(Less)
- author
- 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
- publishing date
- 2017-07-11
- 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
- pmid:28648899
- 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
- 2024-08-05 05:25:47
@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}}, keywords = {{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}}, doi = {{10.1016/j.stemcr.2017.05.025}}, volume = {{9}}, year = {{2017}}, }