GATA2 Promotes Hematopoietic Development and Represses Cardiac Differentiation of Human Mesoderm
2019; Elsevier BV; Volume: 13; Issue: 3 Linguagem: Inglês
10.1016/j.stemcr.2019.07.009
ISSN2213-6711
AutoresJulio Castaño, Sergi Aranda, Clara Bueno, Fernando J. Calero‐Nieto, Eva Mejía-Ramírez, José Luis Mosquera, Enrique Blanco, Xiaonan Wang, Cristina Prieto, Lorea Zabaleta, Elisabetta Mereu, Meritxell Rovira, Senda Jiménez‐Delgado, Daniel R. Matson, Holger Heyn, Emery H. Bresnick, Berthold Göttgens, Luciano Di Croce, Pablo Menéndez, Ángel Raya, Alessandra Giorgetti,
Tópico(s)Pluripotent Stem Cells Research
ResumoHighlights•GATA2 promotes hemogenic emergence during human iPSC differentiation•GATA2 enhances hematopoietic differentiation of human iPSCs•GATA2 acts as a direct repressor of cardiac fates during mesoderm specificationSummaryIn 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.Graphical abstract
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