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The onset of circulation triggers a metabolic switch required for endothelial to hematopoietic transition

Azzoni, Emanuele ; Frontera, Vincent ; Anselmi, Giorgio ; Rode, Christina ; James, Chela ; Deltcheva, Elitza M. ; Demian, Atanasiu S. ; Brown, John ; Barone, Cristiana and Patelli, Arianna , et al. (2021) In Cell Reports 37(11).
Abstract

Hematopoietic stem cells (HSCs) emerge during development from the vascular wall of the main embryonic arteries. The onset of circulation triggers several processes that provide critical external factors for HSC generation. Nevertheless, it is not fully understood how and when the onset of circulation affects HSC emergence. Here we show that in Ncx1−/− mouse embryos devoid of circulation the HSC lineage develops until the phenotypic pro-HSC stage. However, these cells reside in an abnormal microenvironment, fail to activate the hematopoietic program downstream of Runx1, and are functionally impaired. Single-cell transcriptomics shows that during the endothelial-to-hematopoietic transition, Ncx1−/− cells fail to... (More)

Hematopoietic stem cells (HSCs) emerge during development from the vascular wall of the main embryonic arteries. The onset of circulation triggers several processes that provide critical external factors for HSC generation. Nevertheless, it is not fully understood how and when the onset of circulation affects HSC emergence. Here we show that in Ncx1−/− mouse embryos devoid of circulation the HSC lineage develops until the phenotypic pro-HSC stage. However, these cells reside in an abnormal microenvironment, fail to activate the hematopoietic program downstream of Runx1, and are functionally impaired. Single-cell transcriptomics shows that during the endothelial-to-hematopoietic transition, Ncx1−/− cells fail to undergo a glycolysis to oxidative phosphorylation metabolic switch present in wild-type cells. Interestingly, experimental activation of glycolysis results in decreased intraembryonic hematopoiesis. Our results suggest that the onset of circulation triggers metabolic changes that allow HSC generation to proceed.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cell Reports
volume
37
issue
11
article number
110103
publisher
Cell Press
external identifiers
  • scopus:85121145978
  • pmid:34910918
ISSN
2211-1247
DOI
10.1016/j.celrep.2021.110103
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2021 The Authors
id
486fd6f7-3932-40fc-8a06-a04462a2b265
date added to LUP
2022-01-27 10:04:26
date last changed
2024-03-09 03:02:50
@article{486fd6f7-3932-40fc-8a06-a04462a2b265,
  abstract     = {{<p>Hematopoietic stem cells (HSCs) emerge during development from the vascular wall of the main embryonic arteries. The onset of circulation triggers several processes that provide critical external factors for HSC generation. Nevertheless, it is not fully understood how and when the onset of circulation affects HSC emergence. Here we show that in Ncx1<sup>−/−</sup> mouse embryos devoid of circulation the HSC lineage develops until the phenotypic pro-HSC stage. However, these cells reside in an abnormal microenvironment, fail to activate the hematopoietic program downstream of Runx1, and are functionally impaired. Single-cell transcriptomics shows that during the endothelial-to-hematopoietic transition, Ncx1<sup>−/−</sup> cells fail to undergo a glycolysis to oxidative phosphorylation metabolic switch present in wild-type cells. Interestingly, experimental activation of glycolysis results in decreased intraembryonic hematopoiesis. Our results suggest that the onset of circulation triggers metabolic changes that allow HSC generation to proceed.</p>}},
  author       = {{Azzoni, Emanuele and Frontera, Vincent and Anselmi, Giorgio and Rode, Christina and James, Chela and Deltcheva, Elitza M. and Demian, Atanasiu S. and Brown, John and Barone, Cristiana and Patelli, Arianna and Harman, Joe R. and Nicholls, Matthew and Conway, Simon J. and Morrissey, Edward and Jacobsen, Sten Eirik W. and Sparrow, Duncan B. and Harris, Adrian L. and Enver, Tariq and de Bruijn, Marella F.T.R.}},
  issn         = {{2211-1247}},
  language     = {{eng}},
  month        = {{12}},
  number       = {{11}},
  publisher    = {{Cell Press}},
  series       = {{Cell Reports}},
  title        = {{The onset of circulation triggers a metabolic switch required for endothelial to hematopoietic transition}},
  url          = {{http://dx.doi.org/10.1016/j.celrep.2021.110103}},
  doi          = {{10.1016/j.celrep.2021.110103}},
  volume       = {{37}},
  year         = {{2021}},
}