Fetal hematopoietic stem cell homing is controlled by VEGF regulating the integrity and oxidative status of the stromal-vascular bone marrow niches.
Animals
Bone Marrow
/ metabolism
Bone Marrow Cells
/ cytology
Cell Movement
/ physiology
Cells, Cultured
Hematopoietic Stem Cells
/ metabolism
Mesenchymal Stem Cells
/ metabolism
Mice
Oxidative Stress
/ physiology
Stem Cell Niche
/ physiology
Stem Cell Transplantation
/ methods
Vascular Endothelial Growth Factor A
/ metabolism
VEGF
angiogenesis
bone
bone marrow
hematopoiesis
hematopoietic stem cell
niche
osteoprogenitor
oxidative stress
stromal cell
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
24 08 2021
24 08 2021
Historique:
received:
21
11
2020
revised:
28
05
2021
accepted:
05
08
2021
entrez:
25
8
2021
pubmed:
26
8
2021
medline:
12
2
2022
Statut:
ppublish
Résumé
Hematopoietic stem and progenitor cell (HSPC) engraftment after transplantation during anticancer treatment depends on support from the recipient bone marrow (BM) microenvironment. Here, by studying physiological homing of fetal HSPCs, we show the critical requirement of balanced local crosstalk within the skeletal niche for successful HSPC settlement in BM. Transgene-induced overproduction of vascular endothelial growth factor (VEGF) by osteoprogenitor cells elicits stromal and endothelial hyperactivation, profoundly impacting the stromal-vessel interface and vascular architecture. Concomitantly, HSPC homing and survival are drastically impaired. Transcriptome profiling, flow cytometry, and high-resolution imaging indicate alterations in perivascular and endothelial cell characteristics, vascular function and cellular metabolism, associated with increased oxidative stress within the VEGF-enriched BM environment. Thus, developmental HSPC homing to bone is controlled by local stromal-vascular integrity and the oxidative-metabolic status of the recipient milieu. Interestingly, irradiation of adult mice also induces stromal VEGF expression and similar osteo-angiogenic niche changes, underscoring that our findings may contribute targets for improving stem cell therapies.
Identifiants
pubmed: 34433017
pii: S2211-1247(21)01056-1
doi: 10.1016/j.celrep.2021.109618
pmc: PMC8411121
pii:
doi:
Substances chimiques
Vascular Endothelial Growth Factor A
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
109618Subventions
Organisme : DBT-Wellcome Trust India Alliance
ID : IA/I/15/2/502061
Pays : India
Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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