GATA2 Promotes Hematopoietic Development and Represses Cardiac Differentiation of Human Mesoderm
Por:
Castano, J, Aranda, S, Bueno, C, Calero-Nieto, FJ, Mejia-Ramirez, E, Mosquera, JL, Blanco, E, Wang, X, Prieto, C, Zabaleta, L, Mereu, E, Rovira, M, Jimenez-Delgado, S, Matson, DR, Heyn, H, Bresnick, EH, Gottgens, B, Di Croce, L, Menendez, P, Raya, A and Giorgetti, A
Publicada:
10 sep 2019
Resumen:
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.
Filiaciones:
Castano, J:
Hosp Duran & Reynals, CMRB, Gran Via LHospitalet 199-203, Barcelona 08908, Spain
Ctr Networked Biomed Res Bioengn Biomat & Nanomed, Madrid 28029, Spain
Aranda, S:
Univ Pompeu Fabra, Barcelona Inst Sci & Technol, CRG, Barcelona 08003, Spain
:
Univ Barcelona, Josep Carreras Leukemia Res Inst, E-08036 Barcelona, Spain
Univ Barcelona, Sch Med, Dept Biomed, E-08036 Barcelona, Spain
Calero-Nieto, FJ:
Univ Cambridge, Wellcome & MRC Cambridge Stem Cell Inst, Dept Hematol, Cambridge, England
Univ Cambridge, Cambridge Inst Med Res, Cambridge, England
Mejia-Ramirez, E:
Hosp Duran & Reynals, CMRB, Gran Via LHospitalet 199-203, Barcelona 08908, Spain
Mosquera, JL:
Bellvitge Biomed Res Inst IDIBELL, Bioinformat Unit, Barcelona 08908, Spain
Blanco, E:
Univ Pompeu Fabra, Barcelona Inst Sci & Technol, CRG, Barcelona 08003, Spain
Wang, X:
Univ Cambridge, Wellcome & MRC Cambridge Stem Cell Inst, Dept Hematol, Cambridge, England
Univ Cambridge, Cambridge Inst Med Res, Cambridge, England
Prieto, C:
Univ Barcelona, Josep Carreras Leukemia Res Inst, E-08036 Barcelona, Spain
Univ Barcelona, Sch Med, Dept Biomed, E-08036 Barcelona, Spain
Zabaleta, L:
Fdn Inbiomed, Lab Hematol Dis, San Sebastian 20009, Spain
Mereu, E:
BIST, CRG, CNAG CRG, Barcelona, Spain
Rovira, M:
Hosp Duran & Reynals, CMRB, Gran Via LHospitalet 199-203, Barcelona 08908, Spain
Jimenez-Delgado, S:
Hosp Duran & Reynals, CMRB, Gran Via LHospitalet 199-203, Barcelona 08908, Spain
Matson, DR:
Univ Wisconsin, Sch Med & Publ Hlth, Dept Cell & Regenerat Biol, UW Madison Blood Res Program,Carbone Canc Ctr, Madison, WI 53705 USA
Heyn, H:
BIST, CRG, CNAG CRG, Barcelona, Spain
Univ Pompeu Fabra, Barcelona, Spain
Bresnick, EH:
Univ Wisconsin, Sch Med & Publ Hlth, Dept Cell & Regenerat Biol, UW Madison Blood Res Program,Carbone Canc Ctr, Madison, WI 53705 USA
Gottgens, B:
Univ Barcelona, Josep Carreras Leukemia Res Inst, E-08036 Barcelona, Spain
Univ Barcelona, Sch Med, Dept Biomed, E-08036 Barcelona, Spain
Di Croce, L:
Univ Pompeu Fabra, Barcelona Inst Sci & Technol, CRG, Barcelona 08003, Spain
ICREA, Barcelona 08010, Spain
:
Univ Barcelona, Josep Carreras Leukemia Res Inst, E-08036 Barcelona, Spain
Univ Barcelona, Sch Med, Dept Biomed, E-08036 Barcelona, Spain
ICREA, Barcelona 08010, Spain
Ctr Invest Biomed Red Canc CIBERONIC ISCIII, Barcelona, Spain
Raya, A:
Ctr Networked Biomed Res Bioengn Biomat & Nanomed, Madrid 28029, Spain
ICREA, Barcelona 08010, Spain
Giorgetti, A:
Hosp Duran & Reynals, CMRB, Gran Via LHospitalet 199-203, Barcelona 08908, Spain
Green Published, Green Submitted, gold
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