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Endothelial-specific Gata3 expression is required for hematopoietic stem cell generation

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 proce...

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Autores principales: Zaidan, Nada, Nitsche, Leslie, Diamanti, Evangelia, Hannah, Rebecca, Fidanza, Antonella, Wilson, Nicola K., Forrester, Lesley M., Göttgens, Berthold, Ottersbach, Katrin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9391417/
https://www.ncbi.nlm.nih.gov/pubmed/35905741
http://dx.doi.org/10.1016/j.stemcr.2022.06.008
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author Zaidan, Nada
Nitsche, Leslie
Diamanti, Evangelia
Hannah, Rebecca
Fidanza, Antonella
Wilson, Nicola K.
Forrester, Lesley M.
Göttgens, Berthold
Ottersbach, Katrin
author_facet Zaidan, Nada
Nitsche, Leslie
Diamanti, Evangelia
Hannah, Rebecca
Fidanza, Antonella
Wilson, Nicola K.
Forrester, Lesley M.
Göttgens, Berthold
Ottersbach, Katrin
author_sort Zaidan, Nada
collection PubMed
description 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.
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spelling pubmed-93914172022-08-21 Endothelial-specific Gata3 expression is required for hematopoietic stem cell generation Zaidan, Nada Nitsche, Leslie Diamanti, Evangelia Hannah, Rebecca Fidanza, Antonella Wilson, Nicola K. Forrester, Lesley M. Göttgens, Berthold Ottersbach, Katrin Stem Cell Reports Report 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. Elsevier 2022-07-28 /pmc/articles/PMC9391417/ /pubmed/35905741 http://dx.doi.org/10.1016/j.stemcr.2022.06.008 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Report
Zaidan, Nada
Nitsche, Leslie
Diamanti, Evangelia
Hannah, Rebecca
Fidanza, Antonella
Wilson, Nicola K.
Forrester, Lesley M.
Göttgens, Berthold
Ottersbach, Katrin
Endothelial-specific Gata3 expression is required for hematopoietic stem cell generation
title Endothelial-specific Gata3 expression is required for hematopoietic stem cell generation
title_full Endothelial-specific Gata3 expression is required for hematopoietic stem cell generation
title_fullStr Endothelial-specific Gata3 expression is required for hematopoietic stem cell generation
title_full_unstemmed Endothelial-specific Gata3 expression is required for hematopoietic stem cell generation
title_short Endothelial-specific Gata3 expression is required for hematopoietic stem cell generation
title_sort endothelial-specific gata3 expression is required for hematopoietic stem cell generation
topic Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9391417/
https://www.ncbi.nlm.nih.gov/pubmed/35905741
http://dx.doi.org/10.1016/j.stemcr.2022.06.008
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