Journal Article

DKFZ-2022-01514

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Inflammatory exposure drives long-lived impairment of hematopoietic stem cell self-renewal activity and accelerated aging.

Bogeska, R. (First author)DKFZ* ; Mikecin, A.-M.DKFZ* ; Kaschutnig, P. E.DKFZ* ; Fawaz, M. ; Büchler-Schäff, M.DKFZ* ; Le, D. ; Ganuza, M. ; Vollmer, A. ; Paffenholz, S.DKFZ* ; Asada, N. ; Rodriguez-Correa, E.DKFZ* ; Frauhammer, F.DKFZ* ; Büttner, F.DKFZ* ; Ball, M.DKFZ* ; Knoch, J.DKFZ* ; Stäble, S.DKFZ* ; Walter, D.DKFZ* ; Petri, A.DKFZ* ; Carreño-Gonzalez, M. J.DKFZ* ; Wagner, V.DKFZ* ; Brors, B.DKFZ* ; Haas, S.DKFZ* ; Lipka, D.DKFZ* ; Essers, M.DKFZ* ; Weru, V.DKFZ* ; Holland-Letz, T.DKFZ* ; Mallm, J.-P.DKFZ* ; Rippe, K.DKFZ* ; Krämer, S.DKFZ* ; Schlesner, M.DKFZ* ; McKinney Freeman, S. ; Florian, M. C. ; King, K. Y. ; Frenette, P. S. ; Rieger, M. A.DKFZ* ; Milsom, M. (Last author)DKFZ*

2022
Elsevier Amsterdam [u.a.]

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Please use a persistent id in citations: doi:10.1016/j.stem.2022.06.012

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.

Keyword(s): HSCs ; accelerated aging ; aging ; clonal hematopoiesis ; hematopoietic stem cells ; inflammaging ; inflammation ; self-renewal ; stem cell exhaustion ; stress hematopoiesis

Note: DKFZ-ZMBH Alliance / #EA:A012#LA:A012# / 2022 Aug 4;29(8):1273-1284.e8

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Contributing Institute(s):

1. A012 Experimentelle Hämatologie (A012)
2. Angewandte Bioinformatik (B330)
3. DKTK HD zentral (HD01)
4. Translationale Medizinische Onkologie (B340)
5. A010 Stammzellen und Krebs (A010)
6. A011 Stressinduzierte Aktivierung von Hämatopeotischen Stammzellen (A011)
7. C060 Biostatistik (C060)
8. B066 Chromatin-Netzwerke (B066)
9. Bioinformatik und Omics Data Analytics (B240)
10. DKTK Koordinierungsstelle Frankfurt (FM01)

Research Program(s):

1. 311 - Zellbiologie und Tumorbiologie (POF4-311) (POF4-311)

Appears in the scientific report 2022

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Essential Science Indicators ; IF >= 25 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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