Endothelial-specific Gata3 expression is required for hematopoietic stem cell generation.
Authors
Zaidan, Nada
Nitsche, Leslie
Diamanti, Evangelia
Hannah, Rebecca
Fidanza, Antonella
Wilson, Nicola K
Forrester, Lesley M
Göttgens, Berthold
Ottersbach, Katrin
Publication Date
2022-08-09Journal Title
Stem Cell Reports
ISSN
2213-6711
Publisher
Elsevier BV
Type
Article
This Version
AM
Metadata
Show full item recordCitation
Zaidan, N., Nitsche, L., Diamanti, E., Hannah, R., Fidanza, A., Wilson, N. K., Forrester, L. M., et al. (2022). Endothelial-specific Gata3 expression is required for hematopoietic stem cell generation.. Stem Cell Reports https://doi.org/10.1016/j.stemcr.2022.06.008
Abstract
To generate sufficient numbers of transplantable hematopoietic stem cells (HSCs) in vitro, a detailed understanding of how this process takes place in vivo is essential. The endothelial-to-hematopoietic transition (EHT), which culminates in the production of the first HSCs, is a highly complex process during which key regulators are switched on and off at precise moments, and that is embedded into a myriad of microenvironmental signals from surrounding cells and tissues. We have previously demonstrated an HSC-supportive function for GATA3 within the sympathetic nervous system and the sub-aortic mesenchyme, but show here that it also plays a cell-intrinsic role during the EHT. It is expressed in hemogenic endothelial cells and early HSC precursors, where its expression correlates with a more quiescent state. Importantly, endothelial-specific deletion of Gata3 shows that it is functionally required for these cells to mature into HSCs, placing GATA3 at the core of the EHT regulatory network.
Keywords
Cdkn1c, Gata3, aorta-gonads-mesonephros, cell cycle, endothelial-to-hematopoietic transition, hematopoietic stem cell, hemogenic endothelial cells, p57Kip2, Cell Differentiation, Endothelium, Gonads, Hemangioblasts, Hematopoiesis, Hematopoietic Stem Cells, Mesoderm, Mesonephros
Sponsorship
Wellcome Trust (203151/Z/16/Z)
Wellcome Trust (203151/A/16/Z)
Medical Research Council (MC_PC_17230)
Identifiers
External DOI: https://doi.org/10.1016/j.stemcr.2022.06.008
This record's URL: https://www.repository.cam.ac.uk/handle/1810/338759
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