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

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Item Type:	Article
Title:	Inflammatory exposure drives long-lived impairment of hematopoietic stem cell self-renewal activity and accelerated aging
Creators Name:	Bogeska, R., Mikecin, A.M., Kaschutnig, P., Fawaz, M., Büchler-Schäff, M., Le, D., Ganuza, M., Vollmer, A., Paffenholz, S.V., Asada, N., Rodriguez-Correa, E., Frauhammer, F., Buettner, F., Ball, M., Knoch, J., Stäble, S., Walter, D., Petri, A., Carreño-Gonzalez, M.J., Wagner, V., Brors, B., Haas, S., Lipka, D.B., Essers, M.A.G., Weru, V., Holland-Letz, T., Mallm, J.P., Rippe, K., Krämer, S., Schlesner, M., McKinney Freeman, S., Florian, M.C., King, K.Y., Frenette, P.S., 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
Date:	4 August 2022
Additional Information:	Copyright © 2022 Elsevier Inc. All rights reserved.
Official Publication:	https://doi.org/10.1016/j.stem.2022.06.012
External Fulltext:	View full text on PubMed Central
PubMed:	View item in PubMed

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