title: Gata2 is required for HSC generation and survival.
abstract: Knowledge of the key transcription factors that drive hematopoietic stem cell (HSC) generation is of particular importance for current hematopoietic regenerative approaches and reprogramming strategies. Whereas GATA2 has long been implicated as a hematopoietic transcription factor and its dysregulated expression is associated with human immunodeficiency syndromes and vascular integrity, it is as yet unknown how GATA2 functions in the generation of HSCs. HSCs are generated from endothelial cells of the major embryonic vasculature (aorta, vitelline, and umbilical arteries) and are found in intra-aortic hematopoietic clusters. In this study, we find that GATA2 function is essential for the generation of HSCs during the stage of endothelial-to-hematopoietic cell transition. Specific deletion of Gata2 in Vec (Vascular Endothelial Cadherin)-expressing endothelial cells results in a deficiency of long-term repopulating HSCs and intra-aortic cluster cells. By specific deletion of Gata2 in Vav-expressing hematopoietic cells (after HSC generation), we further show that GATA2 is essential for HSC survival. This is in contrast to the known activity of the RUNX1 transcription factor, which functions only in the generation of HSCs, and highlights the unique requirement for GATA2 function in HSCs throughout all developmental stages.
authors.affiliation: Erasmus Medical Center, Erasmus Stem Cell Institute, 3000 CA Rotterdam, Netherlands.
authors.forename: Emma
authors.initials: E
authors.lastname: de Pater
authors.forename: Polynikis
authors.initials: P
authors.lastname: Kaimakis
authors.forename: Chris S
authors.initials: CS
authors.lastname: Vink
authors.forename: Tomomasa
authors.initials: T
authors.lastname: Yokomizo
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yamada-Inagawa
authors.forename: Reinier
authors.initials: R
authors.lastname: van der Linden
authors.forename: Parham Solaimani
authors.initials: PS
authors.lastname: Kartalaei
authors.forename: Sally A
authors.initials: SA
authors.lastname: Camper
authors.forename: Nancy
authors.initials: N
authors.lastname: Speck
authors.forename: Elaine
authors.initials: E
authors.lastname: Dzierzak
mesh_terms: D000483:Alleles; D000818:Animals; D017209:Apoptosis; D002469:Cell Separation; D002470:Cell Survival; D005434:Flow Cytometry; D050989:GATA2 Transcription Factor / Q000502:physiology*; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D013234:Stem Cells
chemical_list: D050989:GATA2 Transcription Factor; C494712:Gata2 protein, mouse