title: New insights into the regulation by RUNX1 and GFI1(s) proteins of the endothelial to hematopoietic transition generating primordial hematopoietic cells.
abstract: The first hematopoietic cells are generated very early in ontogeny to support the growth of the embryo and to provide the foundation to the adult hematopoietic system. There is a considerable therapeutic interest in understanding how these first blood cells are generated in order to try to reproduce this process in vitro. This would allow generating blood products, or hematopoietic cell populations from embryonic stem (ES) cells, induced pluripotent stem cells or through directed reprogramming. Recent studies have clearly established that the first hematopoietic cells originate from a hemogenic endothelium (HE) through an endothelial to hematopoietic transition (EHT). The molecular mechanisms underlining this transition remain largely unknown with the exception that the transcription factor RUNX1 is critical for this process. In this Extra Views report, we discuss our recent studies demonstrating that the transcriptional repressors GFI1 and GFI1B have a critical role in the EHT. We established that these RUNX1 transcriptional targets are actively implicated in the downregulation of the endothelial program and the loss of endothelial identity during the formation of the first blood cells. In addition, our results suggest that GFI1 expression provides an ideal novel marker to identify, isolate and study the HE cell population.
authors.affiliation: a CRUK Stem Cell Biology, Cancer Research UK Manchester Institute , Manchester , UK.
authors.forename: Roshana
authors.initials: R
authors.lastname: Thambyrajah
authors.affiliation: a CRUK Stem Cell Biology, Cancer Research UK Manchester Institute , Manchester , UK.
authors.forename: Rahima
authors.initials: R
authors.lastname: Patel
authors.affiliation: a CRUK Stem Cell Biology, Cancer Research UK Manchester Institute , Manchester , UK.
authors.forename: Milena
authors.initials: M
authors.lastname: Mazan
authors.affiliation: a CRUK Stem Cell Biology, Cancer Research UK Manchester Institute , Manchester , UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Lie-A-Ling
authors.affiliation: b CRUK Stem Cell Haematopoiesis, Cancer Research UK Manchester Institute , Manchester , UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Lilly
authors.affiliation: b CRUK Stem Cell Haematopoiesis, Cancer Research UK Manchester Institute , Manchester , UK.
authors.forename: Alexia
authors.initials: A
authors.lastname: Eliades
authors.affiliation: b CRUK Stem Cell Haematopoiesis, Cancer Research UK Manchester Institute , Manchester , UK.
authors.forename: Sara
authors.initials: S
authors.lastname: Menegatti
authors.affiliation: b CRUK Stem Cell Haematopoiesis, Cancer Research UK Manchester Institute , Manchester , UK.
authors.forename: Eva
authors.initials: E
authors.lastname: Garcia-Alegria
authors.affiliation: a CRUK Stem Cell Biology, Cancer Research UK Manchester Institute , Manchester , UK.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Florkowska
authors.affiliation: a CRUK Stem Cell Biology, Cancer Research UK Manchester Institute , Manchester , UK.
authors.forename: Kiran
authors.initials: K
authors.lastname: Batta
authors.affiliation: b CRUK Stem Cell Haematopoiesis, Cancer Research UK Manchester Institute , Manchester , UK.
authors.forename: Valerie
authors.initials: V
authors.lastname: Kouskoff
authors.affiliation: a CRUK Stem Cell Biology, Cancer Research UK Manchester Institute , Manchester , UK.
authors.forename: Georges
authors.initials: G
authors.lastname: Lacaud
mesh_terms: D000818:Animals; D050676:Core Binding Factor Alpha 2 Subunit / Q000378:metabolism*; D055018:Hemangioblasts / Q000378:metabolism*; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D008954:Models, Biological; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D014157:Transcription Factors
keywords: EHT (endothelial to hematopoietic transition); ES cells; GFI1; GFI1B; HSCs (Hematopoietic stem cells); RUNX1; development; hematopoiesis; hemogenic endothelium; reprogramming