Glutamine metabolism regulates endothelial to hematopoietic transition and hematopoietic lineage specification

Abstract During hematopoietic development, definitive hematopoietic cells are derived from hemogenic endothelial (HE) cells through a process known as endothelial to hematopoietic transition (EHT). During EHT, transitioning cells proliferate and undergo progressive changes in gene expression culmina...

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Autores principales:	Leal Oburoglu, Els Mansell, Niels-Bjarne Woods
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0c94bcf28917495fa2414c4ac96492f7
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id	oai:doaj.org-article:0c94bcf28917495fa2414c4ac96492f7
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spelling	oai:doaj.org-article:0c94bcf28917495fa2414c4ac96492f72021-12-02T17:51:21ZGlutamine metabolism regulates endothelial to hematopoietic transition and hematopoietic lineage specification10.1038/s41598-021-97194-72045-2322https://doaj.org/article/0c94bcf28917495fa2414c4ac96492f72021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97194-7https://doaj.org/toc/2045-2322Abstract During hematopoietic development, definitive hematopoietic cells are derived from hemogenic endothelial (HE) cells through a process known as endothelial to hematopoietic transition (EHT). During EHT, transitioning cells proliferate and undergo progressive changes in gene expression culminating in the new cell identity with corresponding changes in function, phenotype and morphology. However, the metabolic pathways fueling this transition remain unclear. We show here that glutamine is a crucial regulator of EHT and a rate limiting metabolite in the hematopoietic differentiation of HE cells. Intriguingly, different hematopoietic lineages require distinct derivatives of glutamine. While both derivatives, α-ketoglutarate and nucleotides, are required for early erythroid differentiation of HE during glutamine deprivation, lymphoid differentiation relies on α-ketoglutarate alone. Furthermore, treatment of HE cells with α-ketoglutarate in glutamine-free conditions pushes their differentiation towards lymphoid lineages both in vitro and in vivo, following transplantation into NSG mice. Thus, we report an essential role for glutamine metabolism during EHT, regulating both the emergence and the specification of hematopoietic cells through its various derivatives.Leal OburogluEls MansellNiels-Bjarne WoodsNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Leal Oburoglu Els Mansell Niels-Bjarne Woods Glutamine metabolism regulates endothelial to hematopoietic transition and hematopoietic lineage specification
description	Abstract During hematopoietic development, definitive hematopoietic cells are derived from hemogenic endothelial (HE) cells through a process known as endothelial to hematopoietic transition (EHT). During EHT, transitioning cells proliferate and undergo progressive changes in gene expression culminating in the new cell identity with corresponding changes in function, phenotype and morphology. However, the metabolic pathways fueling this transition remain unclear. We show here that glutamine is a crucial regulator of EHT and a rate limiting metabolite in the hematopoietic differentiation of HE cells. Intriguingly, different hematopoietic lineages require distinct derivatives of glutamine. While both derivatives, α-ketoglutarate and nucleotides, are required for early erythroid differentiation of HE during glutamine deprivation, lymphoid differentiation relies on α-ketoglutarate alone. Furthermore, treatment of HE cells with α-ketoglutarate in glutamine-free conditions pushes their differentiation towards lymphoid lineages both in vitro and in vivo, following transplantation into NSG mice. Thus, we report an essential role for glutamine metabolism during EHT, regulating both the emergence and the specification of hematopoietic cells through its various derivatives.
format	article
author	Leal Oburoglu Els Mansell Niels-Bjarne Woods
author_facet	Leal Oburoglu Els Mansell Niels-Bjarne Woods
author_sort	Leal Oburoglu
title	Glutamine metabolism regulates endothelial to hematopoietic transition and hematopoietic lineage specification
title_short	Glutamine metabolism regulates endothelial to hematopoietic transition and hematopoietic lineage specification
title_full	Glutamine metabolism regulates endothelial to hematopoietic transition and hematopoietic lineage specification
title_fullStr	Glutamine metabolism regulates endothelial to hematopoietic transition and hematopoietic lineage specification
title_full_unstemmed	Glutamine metabolism regulates endothelial to hematopoietic transition and hematopoietic lineage specification
title_sort	glutamine metabolism regulates endothelial to hematopoietic transition and hematopoietic lineage specification
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/0c94bcf28917495fa2414c4ac96492f7
work_keys_str_mv	AT lealoburoglu glutaminemetabolismregulatesendothelialtohematopoietictransitionandhematopoieticlineagespecification AT elsmansell glutaminemetabolismregulatesendothelialtohematopoietictransitionandhematopoieticlineagespecification AT nielsbjarnewoods glutaminemetabolismregulatesendothelialtohematopoietictransitionandhematopoieticlineagespecification
_version_	1718379269489426432

Glutamine metabolism regulates endothelial to hematopoietic transition and hematopoietic lineage specification

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