The DOI matches its Crossref record; 66 of the 66 references it cites were found in a registry or an index.
Inflammatory exposure drives long-lived impairment of hematopoietic stem cell self-renewal activity and accelerated aging
Open accessPublished version of a preprint
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.
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“Moreover, Bogeska et al. showed that inflammatory exposure induces long-term impairment of HSC self-renewal and accelerates their functional aging, contributing to persistent immune dysregulation [83].”
From Chronic Stress and Autoimmunity: The Role of HPA Axis and Cortisol Dysregulation (2025) · cites this paper as [83]
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“while repetitive sterile inflammation did not result in major gene expression changes, it resulted in hypomethylation of promoters of inflammatory (particularly interferon) response genes, leading them to conclude that self-renewal is epigenetically regulated in this model.”
From Clonal hematopoiesis and inflammation – the perpetual cycle (2023) · cites this paper as [65]
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“Inflammation drives impaired self-renewal activity and accelerates aging of HSCs. Exposure to inflammatory stimuli during the early to mid-life stages in mice can lead to the eventual development of peripheral blood hemocytopenia, bone marrow (BM) cytopenia, and BM adipocyte accumulation, features that together constitute typical features of hematopoiesis in the elderly.17”
From Inflammation and aging: signaling pathways and intervention therapies (2023) · cites this paper as [17]
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“Chronic pro-inflammatory signaling due to chronic infections or repetitive sterile inflammation, however, has been shown to be detrimental to HSPC self-renewal, promoting loss of quiescence and differentiation [61–65].”
From Clonal hematopoiesis and inflammation – the perpetual cycle (2023) · cites this paper as [65]
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“the authors showed that the demise of the functional stem cell population was not due to systemic inhibitory effects of inflammation on hematopoiesis but was due to increased proliferation of HSPCs, as label-retaining long-term HSPCs did not lose their repopulating capacity with chronic inflammation [65].”
From Clonal hematopoiesis and inflammation – the perpetual cycle (2023) · cites this paper as [65]
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Citations
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Cited by
Sorted by citations
Inflammation and aging: signaling pathways and intervention therapies
Li, X., Li, C., Zhang, W., Wang, Y., Qian, P., & Huang, H. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01502-8 · Cited by 1,443
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Metadata
- Authors
- 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., & Milsom, M. D.
- Affiliations
- German Cancer Research Center (DE)
- University Hospital Frankfurt (DE)
- Baylor College of Medicine (US)
- St. Jude Children's Research Hospital (US)
- Universität Ulm (DE)
- Albert Einstein College of Medicine (US)
- University of Augsburg (DE)
- Institut d'Investigació Biomédica de Bellvitge (ES)
- Goethe University Frankfurt (DE)
- Corresponding author
- Milsom, Michael D.
- ORCID
- Bogeska, Ruzhica
- Mikecin, Ana-Matea
- Le, Duy
- Ganuza, Miguel
- Asada, Noboru
- Rodriguez-Correa, Esther
- Buettner, Florian
- Stäble, Sina
- Carreño-Gonzalez, Martha J.
- Brors, Benedikt
- Haas, Simon
- Lipka, Daniel B.
- Essers, Marieke A.G.
- Weru, Vivienn
- Mallm, Jan-Philipp
- Rippe, Karsten
- Schlesner, Matthias
- Florian, Maria Carolina
- King, Katherine Y.
- Frenette, Paul S.
- Rieger, Michael A.
- Milsom, Michael D.
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2022-08
- Volume
- 29
- Issue
- 8
- Pages
- 1273-1284.e8
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- PMC
- PMC9357150
- OpenAlex
- W4286254590
- Cited by
- 299
- References
- 66
- Citations by year
- 2026: 67 · 2025: 88 · 2024: 56 · 2023: 60 · 2022: 16
- FWCI
- 40.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 368 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell stem cell (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
- Queen Mary Research Online (Queen Mary University of London) (submittedVersion)
- OPUS (Augsburg University) (submittedVersion, cc-by-nc-nd)
- Funders
- Deutsches Krebsforschungszentrum
- Medical Research Council (MR/V009222/1)
- National Heart, Lung, and Blood Institute (F31HL154661, R35HL155672)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK112976, R01DK056638)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
- Health Sciences › Medicine › Hematology › Blood disorders and treatments
- Keywords
- hematopoietic stem cells, HSC self-renewal, inflammation, bacterial infection, accelerated aging, HSC depletion, bone marrow aging, tissue regeneration
- MeSH terms
- Aged, Aging, Animals, Bone Marrow, Hematopoiesis, Hematopoietic Stem Cells, Humans, Inflammation, Mice
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