biostudies-literatureBogeska RNIDDK NIH HHSNIEHS NIH HHSNHLBI NIH HHS1273-1284.e8https://www.ebi.ac.uk/biostudies/studies/S-EPMC9357150biostudies-literatureUnknown29(8)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 bCell stem cellInflammatory exposure drives long-lived impairment of hematopoietic stem cell self-renewal activity and accelerated aging.PMC9357150R01 DK112976R35 HL155672P30 ES030285R01 DK056638F31 HL154661Asada NLipka DBEssers MAGHolland-Letz TCarreno-Gonzalez MJSchlesner MMcKinney Freeman SRippe KPaffenholz SVKaschutnig PFawaz MBrors BFrenette PSBogeska RLe DGanuza MWeru VMikecin AMHaas SBuettner FWalter DBall MFrauhammer FKramer SKnoch JKing KYMallm JPMilsom MDRodriguez-Correa ERieger MABuchler-Schaff MPetri AWagner VVollmer AFlorian MCStable SfalseInflammatory exposure drives long-lived impairment of hematopoietic stem cell self-renewal activity and accelerated aging.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 b2022-01-01T00:00:00Z2022 Aug2026-04-08T19:48:18.758Z2026-04-08T14:30:08.191ZS-EPMC93571503585861810.1016/j.stem.2022.06.012