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GATA2 Promotes Hematopoietic Development and Represses Cardiac Differentiation of Human Mesoderm.

Accepted version
Peer-reviewed

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Authors

Castaño, Julio 
Aranda, Sergi 
Bueno, Clara 
Calero-Nieto, Fernando J 
Mejia-Ramirez, Eva 

Abstract

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.

Description

Keywords

GATA2, cardiac development, hematopoiesis, hemogenic specification, human iPSCs, mesoderm diversification, Cell Differentiation, GATA2 Transcription Factor, Gene Expression Regulation, Hemangioblasts, Hematopoiesis, Humans, Induced Pluripotent Stem Cells, Mesoderm, Myocytes, Cardiac, Protein Binding, Single-Cell Analysis

Journal Title

Stem Cell Reports

Conference Name

Journal ISSN

2213-6711
2213-6711

Volume Title

13

Publisher

Elsevier BV

Rights

All rights reserved
Sponsorship
Wellcome Trust (079895/Z/06/Z)
Cancer Research UK (21762)
National Institute of Diabetes and Digestive and Kidney Diseases (R24DK106766)
Wellcome Trust (206328/Z/17/Z)
Wellcome Trust (203151/Z/16/Z)
Medical Research Council (MC_PC_12009)
Ramón y Cajal Program, Spanish Ministry of Economy, Industry, and Competitiveness, Spanish Cancer Association, FERO, Instituto de Salud Carlos III, European Social Fund, MINECO, PERIS Program of the Generalitat de Catalunya, Obra Social la Caixa-Fundacion Josep Carreras, Spanish Institute of Health Carlos III, Wellcome Trust, MRC, CRUK, NIH-NIDDK