Giorgetti Alessandra
Center of Regenerative Medicine in Barcelona CMR[B], Spain
Title: GATA2 directly represses cardiac fates to promote hematopoietic specification of human mesoderm
Biography:
Alessandra Giorgetti has completed a Bachelor in Biology (1998) and PhD in Molecular Medicine from the University of Milan, Italy. She has pursued Postdoctoral training at the GMP facility, Ospedale Maggiore Policlinico Milano and in Dr. Rafii’s group at Weill Cornell Medical College in New York from 2004 to 2008, where she acquired invaluable expertise in human hematopoietic stem cells, with a particular interest on cord blood stem cells (CBSCs).Then she joined the CMR[B] as a Research Associate at the Stem Cell Bank from 2008 to 2011. In 2012 she started her period in Inbiomed as head of the Laboratory of Hematopoiesis and Blood Disorders. In 2016 she moved to CMR[B] as a Ramón y Cajal researcher and her long-term goal is to identify developmental pathways that are involved in blood stem cells (hematopoietic stem cells, HSCs) specification during early stage of human embryo development, to direct the differentiation of human induced pluripotent stem cells (iPSCs) into clinically relevant blood stem cells.
Abstract:
In vertebrates, GATA2 is a master regulator of hematopoiesis, repeatedly used throughout embryo development and the adult life. Although it is well established that GATA2 is essential for the onset of mouse hematopoiesis, its role during early human hematopoietic development remains elusive. By combining time-controlled overexpression of GATA2 with genetic knockout experiments, we found that GATA2, at the mesoderm specification stage, promotes the generation of hemo-genic progenitors and their further differentiation to hematopoietic progenitor cells, while negatively regulating cardiac differentiation. Surprisingly, genome-wide transcriptional and chromatin immune-precipitation analysis showed that GATA2 bound preferentially to regulatory regions, and repressed expression, of cardiac development-related genes. In contrast, genes important for hematopoietic differentiation were up-regulated by GATA2 in a mostly indirect manner. Collectively, our data reveal a previously unsuspected role of GATA2 as a direct repressor of cardiac fates, and highlight the importance of coordinating the specification and repression of alternative cell fates.