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Inflammatory exposure drives long-lived impairment of hematopoietic stem cell self-renewal activity and accelerated aging

Item Type:Article
Title:Inflammatory exposure drives long-lived impairment of hematopoietic stem cell self-renewal activity and accelerated aging
Creators Name:Bogeska, R. and Mikecin, A.M. and Kaschutnig, P. and Fawaz, M. and Büchler-Schäff, M. and Le, D. and Ganuza, M. and Vollmer, A. and Paffenholz, S.V. and Asada, N. and Rodriguez-Correa, E. and Frauhammer, F. and Buettner, F. and Ball, M. and Knoch, J. and Stäble, S. and Walter, D. and Petri, A. and Carreño-Gonzalez, M.J. and Wagner, V. and Brors, B. and Haas, S. and Lipka, D.B. and Essers, M.A.G. and Weru, V. and Holland-Letz, T. and Mallm, J.P. and Rippe, K. and Krämer, S. and Schlesner, M. and McKinney Freeman, S. and Florian, M.C. and King, K.Y. and Frenette, P.S. and Rieger, M.A. and Milsom, M.D.
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.
Keywords:Hematopoietic Stem Cells, HSCs, Inflammation, Stress Hematopoiesis, Aging, Clonal Hematopoiesis, Self-Renewal, Accelerated Aging, Stem Cell Exhaustion, Inflammaging, Animals, Mice
Source:Cell Stem Cell
ISSN:1934-5909
Publisher:Cell Press
Volume:29
Number:8
Page Range:1273-1284.e8
Date:4 August 2022
Official Publication:https://doi.org/10.1016/j.stem.2022.06.012
PubMed:View item in PubMed

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