Inflammatory exposure drives long-lived impairment of hematopoietic stem cell self-renewal activity and accelerated aging.
HSCs
accelerated aging
aging
clonal hematopoiesis
hematopoietic stem cells
inflammaging
inflammation
self-renewal
stem cell exhaustion
stress hematopoiesis
Journal
Cell stem cell
ISSN: 1875-9777
Titre abrégé: Cell Stem Cell
Pays: United States
ID NLM: 101311472
Informations de publication
Date de publication:
04 08 2022
04 08 2022
Historique:
received:
19
04
2022
revised:
08
06
2022
accepted:
21
06
2022
pubmed:
21
7
2022
medline:
10
8
2022
entrez:
20
7
2022
Statut:
ppublish
Résumé
Hematopoietic stem cells (HSCs) mediate regeneration of the hematopoietic system following injury, such as following infection or inflammation. These challenges impair HSC function, but whether this functional impairment extends beyond the duration of inflammatory exposure is unknown. Unexpectedly, we observed an irreversible depletion of functional HSCs following challenge with inflammation or bacterial infection, with no evidence of any recovery up to 1 year afterward. HSCs from challenged mice demonstrated multiple cellular and molecular features of accelerated aging and developed clinically relevant blood and bone marrow phenotypes not normally observed in aged laboratory mice but commonly seen in elderly humans. In vivo HSC self-renewal divisions were absent or extremely rare during both challenge and recovery periods. The progressive, irreversible attrition of HSC function demonstrates that temporally discrete inflammatory events elicit a cumulative inhibitory effect on HSCs. This work positions early/mid-life inflammation as a mediator of lifelong defects in tissue maintenance and regeneration.
Identifiants
pubmed: 35858618
pii: S1934-5909(22)00261-2
doi: 10.1016/j.stem.2022.06.012
pmc: PMC9357150
mid: NIHMS1824968
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1273-1284.e8Subventions
Organisme : NHLBI NIH HHS
ID : F31 HL154661
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK112976
Pays : United States
Organisme : NHLBI NIH HHS
ID : R35 HL155672
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES030285
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK056638
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2022 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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