Inflammatory exposure drives long-lived impairment of hematopoietic stem cell self-renewal activity and accelerated aging.
Cell Stem Cell
; 29(8): 1273-1284.e8, 2022 08 04.
Article
em En
| MEDLINE
| ID: mdl-35858618
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Hematopoéticas
/
Hematopoese
Limite:
Aged
/
Animals
/
Humans
Idioma:
En
Revista:
Cell Stem Cell
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Alemanha