GATA2 Promotes Hematopoietic Development and Represses Cardiac Differentiation of Human Mesoderm.
GATA2
cardiac development
hematopoiesis
hemogenic specification
human iPSCs
mesoderm diversification
Journal
Stem cell reports
ISSN: 2213-6711
Titre abrégé: Stem Cell Reports
Pays: United States
ID NLM: 101611300
Informations de publication
Date de publication:
10 09 2019
10 09 2019
Historique:
received:
03
05
2018
revised:
12
07
2019
accepted:
15
07
2019
pubmed:
14
8
2019
medline:
19
6
2020
entrez:
13
8
2019
Statut:
ppublish
Résumé
In vertebrates, GATA2 is a master regulator of hematopoiesis and is expressed throughout embryo development and in adult life. Although the essential role of GATA2 in mouse hematopoiesis is well established, its involvement during early human hematopoietic development is not clear. By combining time-controlled overexpression of GATA2 with genetic knockout experiments, we found that GATA2, at the mesoderm specification stage, promotes the generation of hemogenic endothelial progenitors and their further differentiation to hematopoietic progenitor cells, and negatively regulates cardiac differentiation. Surprisingly, genome-wide transcriptional and chromatin immunoprecipitation analysis showed that GATA2 bound to regulatory regions, and repressed the expression of cardiac development-related genes. Moreover, genes important for hematopoietic differentiation were upregulated by GATA2 in a mostly indirect manner. Collectively, our data reveal a hitherto unrecognized role of GATA2 as a repressor of cardiac fates, and highlight the importance of coordinating the specification and repression of alternative cell fates.
Identifiants
pubmed: 31402335
pii: S2213-6711(19)30261-9
doi: 10.1016/j.stemcr.2019.07.009
pmc: PMC6742600
pii:
doi:
Substances chimiques
GATA2 Transcription Factor
0
GATA2 protein, human
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
515-529Subventions
Organisme : Medical Research Council
ID : MC_PC_12009
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 206328/Z/17/Z
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : T32 HL007899
Pays : United States
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Cancer Research UK
Pays : United Kingdom
Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
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