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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Inflammatory exposure induces long-term impairment of HSC self-renewal and accelerates their functional aging, contributing to persistent immune dysregulation.
“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]
The Results report that inflammatory challenges caused lasting HSC functional decline and that LT-HSCs failed to self-renew during challenge and recovery. The Discussion reports accelerated HSC aging and later blood and bone-marrow abnormalities in exposed mice. It discusses immune suppression as a possible age-associated consequence, but does not establish that the observed HSC changes contributed to persistent immune dysregulation. (LLM, conf=0.83)
Experimental — accuracy not yet measuredRepetitive sterile inflammation results in hypomethylation of promoters of inflammatory response genes, leading to the conclusion that self-renewal is epigenetically regulated in this model.
“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]
The Results section reports no profound sustained gene-expression changes in most LT-HSCs and identifies hypomethylation of promoters of interferon/inflammatory-response genes after inflammatory challenge. It says this demonstrates a lack of self-renewal at the epigenetic level, but does not establish that methylation changes regulate self-renewal; that causal conclusion goes beyond the passage. Page numbers are not available in our copy. (LLM, conf=0.84)
Experimental — accuracy not yet measuredInflammation drives impaired self-renewal activity and accelerates aging of HSCs.
“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]
Chronic pro-inflammatory signaling due to chronic infections or repetitive sterile inflammation is detrimental to HSPC self-renewal, promoting loss of quiescence and differentiation.
“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]
The demise of the functional stem cell population with chronic inflammation is due to increased proliferation of HSPCs, not systemic inhibitory effects of inflammation on hematopoiesis.
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
Love, M. I., Huber, W., & Anders, S. (2014) · Genome Biology · doi:10.1186/s13059-014-0550-8 · Cited by 95,106 · see citing works
Trimmomatic: a flexible trimmer for Illumina sequence data
Bolger, A. M., Lohse, M., & Usadel, B. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btu170 · Cited by 65,548 · see citing works
The Sequence Alignment/Map format and SAMtools
Li, H., Handsaker, B., Wysoker, A., Fennell, T., Ruan, J., Homer, N., Marth, G., Abecasis, G., Durbin, R., & 1000 Genome Project Data Processing Subgroup (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp352 · Cited by 62,041 · see citing works
STAR: ultrafast universal RNA-seq aligner
Dobin, A., Davis, C. A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., Batut, P., Chaisson, M., & Gingeras, T. R. (2013) · Bioinformatics · doi:10.1093/bioinformatics/bts635 · Cited by 51,709 · see citing works
López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013) · Cell · doi:10.1016/j.cell.2013.05.039 · Cited by 14,982 · see citing works
DNA methylation-based biomarkers and the epigenetic clock theory of ageing
Horvath, S., & Raj, K. (2018) · Nature Reviews Genetics · doi:10.1038/s41576-018-0004-3 · Cited by 3,095 · cited 1× · see citing works
“…analysis of the DNA methylome clockinpurifiedLT-HSCs,amethodologythatcanaccuratelypre-dict biological age by evaluating progressive methylation programming events at specific CpG loci and which has recently been linked with the evolution of ARCH in humans (Horvath and Raj, 2018; Nachun et al., 2021).”
Hu, Y., & Smyth, G. K. (2009) · Journal of Immunological Methods · doi:10.1016/j.jim.2009.06.008 · Cited by 2,091 · see citing works
Defining the Epithelial Stem Cell Niche in Skin
Tumbar, T., Guasch, G., Greco, V., Blanpain, C., Lowry, W. E., Rendl, M., & Fuchs, E. (2004) · Science · doi:10.1126/science.1092436 · Cited by 2,031 · see citing works
Wilson, A., Laurenti, E., Oser, G., van der Wath, R. C., Blanco-Bose, W., Jaworski, M., Offner, S., Dunant, C. F., Eshkind, L., Bockamp, E., et al. (2008) · Cell · doi:10.1016/j.cell.2008.10.048 · Cited by 1,908 · see citing works
SC3: consensus clustering of single-cell RNA-seq data
Kiselev, V. Y., Kirschner, K., Schaub, M. T., Andrews, T., Yiu, A., Chandra, T., Natarajan, K. N., Reik, W., Barahona, M., Green, A. R., et al. (2017) · Nature Methods · doi:10.1038/nmeth.4236 · Cited by 1,500 · see citing works
Guralnik, J. M., Eisenstaedt, R. S., Ferrucci, L., Klein, H. G., & Woodman, R. C. (2004) · Blood · doi:10.1182/blood-2004-05-1812 · Cited by 1,450 · see citing works
IFNα activates dormant haematopoietic stem cells in vivo
Essers, M. A. G., Offner, S., Blanco-Bose, W. E., Waibler, Z., Kalinke, U., Duchosal, M. A., & Trumpp, A. (2009) · Nature · doi:10.1038/nature07815 · Cited by 1,368 · see citing works
Self-citationArteriolar niches maintain haematopoietic stem cell quiescence
Kunisaki, Y., Bruns, I., Scheiermann, C., Ahmed, J. U., Pinho, S., Zhang, D., Mizoguchi, T., Wei, Q., Lucas, D., Ito, K., et al. (2013) · Nature · doi:10.1038/nature12612 · Cited by 1,236 · see citing works
Self-citationAccounting for technical noise in single-cell RNA-seq experiments
Brennecke, P., Anders, S., Kim, J. K., Kołodziejczyk, A. A., Zhang, X., Proserpio, V., Baying, B., Benes, V., Teichmann, S. A., Marioni, J. C., et al. (2013) · Nature Methods · doi:10.1038/nmeth.2645 · Cited by 979 · see citing works
Quiescent haematopoietic stem cells are activated by IFN-γ in response to chronic infection
Baldridge, M. T., King, K. Y., Boles, N. C., Weksberg, D. C., & Goodell, M. A. (2010) · Nature · doi:10.1038/nature09135 · Cited by 877 · see citing works
Self-citationCheshier, S. H., Morrison, S. J., Liao, X., & Weissman, I. L. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.6.3120 · Cited by 858 · see citing works
Deconstructing stem cell self-renewal: genetic insights into cell-cycle regulation
Orford, K. W., & Scadden, D. T. (2008) · Nature Reviews Genetics · doi:10.1038/nrg2269 · Cited by 851 · see citing works
Clonal dynamics of native haematopoiesis
Sun, J., Ramos, A., Chapman, B., Johnnidis, J. B., Le, L., Ho, Y.-J., Klein, A. M., Hofmann, O., & Camargo, F. D. (2014) · Nature · doi:10.1038/nature13824 · Cited by 803 · see citing works
Fundamental properties of unperturbed haematopoiesis from stem cells in vivo
Busch, K., Klapproth, K., Barile, M., Flossdorf, M., Holland-Letz, T., Schlenner, S. M., Reth, M., Höfer, T., & Rodewald, H.-R. (2015) · Nature · doi:10.1038/nature14242 · Cited by 769 · see citing works
Self-citationA single-cell resolution map of mouse hematopoietic stem and progenitor cell differentiation
Nestorowa, S., Hamey, F. K., Pijuan Sala, B., Diamanti, E., Shepherd, M., Laurenti, E., Wilson, N. K., Kent, D. G., & Göttgens, B. (2016) · Blood · doi:10.1182/blood-2016-05-716480 · Cited by 768 · see citing works
Pietras, E. M., Mirantes-Barbeito, C., Fong, S., Loeffler, D., Kovtonyuk, L. V., Zhang, S., Lakshminarasimhan, R., Chin, C. P., Techner, J.-M., Will, B., et al. (2016) · Nature Cell Biology · doi:10.1038/ncb3346 · Cited by 689 · see citing works
<i>destiny</i> : diffusion maps for large-scale single-cell data in R
Angerer, P., Haghverdi, L., Büttner, M., Theis, F. J., Marr, C., & Buettner, F. (2016) · Bioinformatics · doi:10.1093/bioinformatics/btv715 · Cited by 640 · see citing works
Self-citationExit from dormancy provokes DNA-damage-induced attrition in haematopoietic stem cells
Walter, D., Lier, A., Geiselhart, A., Thalheimer, F. B., Huntscha, S., Sobotta, M. C., Moehrle, B., Brocks, D., Bayindir, I., Kaschutnig, P., et al. (2015) · Nature · doi:10.1038/nature14131 · Cited by 619 · see citing works
Self-citationAnalysis of histone 2B-GFP retention reveals slowly cycling hematopoietic stem cells
Foudi, A., Hochedlinger, K., Van Buren, D., Schindler, J. W., Jaenisch, R., Carey, V., & Hock, H. (2009) · Nature Biotechnology · doi:10.1038/nbt.1517 · Cited by 586 · see citing works
Inflammatory modulation of HSCs: viewing the HSC as a foundation for the immune response
King, K. Y., & Goodell, M. A. (2011) · Nature reviews. Immunology · doi:10.1038/nri3062 · Cited by 565 · see citing works
Self-citationBeerman, I., Bock, C., Garrison, B. S., Smith, Z. D., Gu, H., Meissner, A., & Rossi, D. J. (2013) · Cell Stem Cell · doi:10.1016/j.stem.2013.01.017 · Cited by 485 · see citing works
Haas, S., Hansson, J., Klimmeck, D., Loeffler, D., Velten, L., Uckelmann, H., Wurzer, S., Prendergast, Á. M., Schnell, A., Hexel, K., et al. (2015) · Cell Stem Cell · doi:10.1016/j.stem.2015.07.007 · Cited by 471 · see citing works
Self-citationVitamin A-Retinoic Acid Signaling Regulates Hematopoietic Stem Cell Dormancy
Cabezas-Wallscheid, N., Buettner, F., Sommerkamp, P., Klimmeck, D., Ladel, L., Thalheimer, F. B., Pastor-Flores, D., Roma, L. P., Renders, S., Zeisberger, P., et al. (2017) · Cell · doi:10.1016/j.cell.2017.04.018 · Cited by 454 · see citing works
Self-citationHematopoietic Cytokines Can Instruct Lineage Choice
Rieger, M. A., Hoppe, P. S., Smejkal, B. M., Eitelhuber, A. C., & Schroeder, T. (2009) · Science · doi:10.1126/science.1171461 · Cited by 404 · cited 1× · see citing works
“Time-lapse imaging and single cell tracking Time-lapse imaging and cell tracking were performed as previously described (Cabezas-Wallscheid et al., 2017; Haetscher et al., 2015; Rieger et al., 2009).”
Self-citationThe integration of inflammaging in age-related diseases
Fülöp, T., Witkowski, J. M., Olivieri, F., & Larbi, A. (2018) · Seminars in Immunology · doi:10.1016/j.smim.2018.09.003 · Cited by 356 · see citing works
Chronic infection drives Dnmt3a-loss-of-function clonal hematopoiesis via IFNγ signaling
Hormaechea-Agulla, D., Matatall, K. A., Le, D. T., Kain, B., Long, X., Kus, P., Jaksik, R., Challen, G. A., Kimmel, M., & King, K. Y. (2021) · Cell Stem Cell · doi:10.1016/j.stem.2021.03.002 · Cited by 329 · see citing works
Self-citationChronic Exposure to a TLR Ligand Injures Hematopoietic Stem Cells
Esplin, B. L., Shimazu, T., Welner, R. S., Garrett, K. P., Nie, L., Zhang, Q., Humphrey, M. B., Yang, Q., Borghesi, L., & Kincade, P. W. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1003438 · Cited by 327 · cited 1× · see citing works
“…stress hematopoiesis can result in functional impairment of HSCs, with observed effects including decreased repo-pulation potential following transplantation and myeloid-skewed differentiation (Esplin et al., 2011; Matatall et al., 2016; Pietras et al., 2016; Takizawa et al., 2017).”
InfluentialPietras, E. M., Lakshminarasimhan, R., Techner, J.-M., Fong, S., Flach, J., Binnewies, M., & Passegué, E. (2014) · Journal of Experimental Medicine · doi:10.1084/jem.20131043 · Cited by 323 · see citing works
Hartsock, R. J., Smith, E. B., & Petty, C. S. (1965) · American Journal of Clinical Pathology · doi:10.1093/ajcp/43.4.326 · Cited by 292 · see citing works
Caiado, F., Pietras, E. M., & Manz, M. G. (2021) · Journal of Experimental Medicine · doi:10.1084/jem.20201541 · Cited by 289 · see citing works
Hematopoietic stem cells count and remember self-renewal divisions
Bernitz, J. M., Kim, H. S., MacArthur, B., Sieburg, H., & Moore, K. (2016) · Cell · doi:10.1016/j.cell.2016.10.022 · Cited by 285 · see citing works
Dynamic variation in cycling of hematopoietic stem cells in steady state and inflammation
Takizawa, H., Regoes, R. R., Boddupalli, C. S., Bonhoeffer, S., & Manz, M. G. (2011) · The Journal of Experimental Medicine · doi:10.1084/jem.20101643 · Cited by 283 · see citing works
Takizawa, H., Fritsch, K., Kovtonyuk, L. V., Saito, Y., Yakkala, C., Jacobs, K., Ahuja, A. K., Lopes, M., Hausmann, A., Hardt, W., et al. (2017) · Cell stem cell · doi:10.1016/j.stem.2017.06.013 · Cited by 272 · see citing works
Biino, G., Santimone, I., Minelli, C., Sorice, R., Frongia, B., Traglia, M., Ulivi, S., Castelnuovo, A. F. D., Gögele, M., Nutile, T., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0054289 · Cited by 265 · see citing works
Chronic Infection Depletes Hematopoietic Stem Cells through Stress-Induced Terminal Differentiation
Matatall, K. A., Jeong, M., Chen, S., Sun, D., Chen, F., Mo, Q., Kimmel, M., & King, K. Y. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.11.031 · Cited by 262 · see citing works
Self-citationHinge, A. S., He, J., Bartram, J., Javier, J. E., Xu, J., Fjellman, E., Sesaki, H., Li, T., Yu, J., Wunderlich, M., et al. (2020) · Cell stem cell · doi:10.1016/j.stem.2020.01.016 · Cited by 199 · cited 1× · see citing works
“This is in line with the overall conclusions of previous work using more severe stress agonists, including chemotherapy and transplantation following myeloablative conditioning, both of which promote extensive HSC proliferation (Beer-man et al., 2013; Hinge et al., 2020).”
Tagmentation-based whole-genome bisulfite sequencing
Wang, Q., Gu, L., Adey, A., Radlwimmer, B., Wang, W., Hovestadt, V., Bähr, M., Wolf, S., Shendure, J., Eils, R., et al. (2013) · Nature Protocols · doi:10.1038/nprot.2013.118 · Cited by 197 · see citing works
Kay, H. E. M. (1965) · The Lancet · doi:10.1016/s0140-6736(65)90763-4 · Cited by 197 · cited 1× · see citing works
“In this context, our data support a clonal succession/generational age model (Kay, 1965; Rosendaal et al., 1976) in which individual HSCs will be sequentially activated to proliferate with each exposure to inflammation, resulting in functional ‘‘exhaustion’’ for these clones.”
Innate immune pathways and inflammation in hematopoietic aging, clonal hematopoiesis, and MDS
Trowbridge, J. J., & Starczynowski, D. T. (2021) · Journal of Experimental Medicine · doi:10.1084/jem.20201544 · Cited by 189 · see citing works
A whole lifespan mouse multi-tissue DNA methylation clock
Meer, M. V., Podolskiy, D. I., Tyshkovskiy, A., & Gladyshev, V. N. (2018) · eLife · doi:10.7554/elife.40675 · Cited by 176 · see citing works
Park, H., Jang, H., Kim, C., Chung, B., Chang, C. L., Park, S. K., & Song, S. (2000) · Journal of Clinical Microbiology · doi:10.1128/jcm.38.11.4080-4085.2000 · Cited by 146 · see citing works
Rodrı́guez, S., Chora, Â. F., Goumnerov, B. C., Mumaw, C. L., Goebel, W. S., Fernández, L., Baydoun, H. E., HogenEsch, H., Dombkowski, D., Karlewicz, C. A., et al. (2009) · Blood · doi:10.1182/blood-2009-04-214916 · Cited by 141 · see citing works
Haematopoietic stem cells in perisinusoidal niches are protected from ageing
Saçma, M., Pospiech, J., Bogeska, R., de Back, W., Mallm, J.-P., Sakk, V., Soller, K., Marka, G., Vollmer, A., Karns, R., et al. (2019) · Nature Cell Biology · doi:10.1038/s41556-019-0418-y · Cited by 133 · see citing works
Self-citationClonal hematopoiesis associated with epigenetic aging and clinical outcomes
Nachun, D. C., Lu, A. T.-H., Bick, A. G., Natarajan, P., Weinstock, J. S., Szeto, M. D., Kathiresan, S., Abecasis, G. R., Taylor, K. D., Guo, X., et al. (2021) · Aging Cell · doi:10.1111/acel.13366 · Cited by 132 · see citing works
Divisional History and Hematopoietic Stem Cell Function during Homeostasis
Qiu, J., Papatsenko, D., Niu, X., Schaniel, C., & Moore, K. A. (2014) · Stem Cell Reports · doi:10.1016/j.stemcr.2014.01.016 · Cited by 131 · see citing works
Tuljapurkar, S. R., McGuire, T. R., Brusnahan, S. K., Jackson, J. D., Garvin, K. L., Kessinger, M. A., Lane, J. T., O’ Kane, B. J., & Sharp, J. G. (2011) · Journal of Anatomy · doi:10.1111/j.1469-7580.2011.01423.x · Cited by 129 · see citing works
The p47 GTPase Lrg-47 (Irgm1) Links Host Defense and Hematopoietic Stem Cell Proliferation
Feng, C. G., Weksberg, D. C., Taylor, G. A., Sher, A., & Goodell, M. A. (2008) · Cell stem cell · doi:10.1016/j.stem.2007.10.007 · Cited by 124 · cited 1× · see citing works
“Mice were infected once per month for 3 months with 2 x 10 6 colony-forming units (CFU) Mycobacterium avium (SmT 2151) by intravenous injection as previously described (Feng et al., 2008).”
OTP: An automatized system for managing and processing NGS data
Reisinger, E., Genthner, L., Kerssemakers, J. N. A., Kensche, P. R., Borufka, S., Jugold, A., Kling, A., Prinz, M., Scholz, I., Zipprich, G., et al. (2017) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2017.08.006 · Cited by 88 · cited 2× · see citing works
“TWGBS sequence alignment and methylation calling Read alignment was performed by the Omics IT and Data Management Core Facility (ODCF) at the German Cancer Research Center using an updated version of the pipeline published by Wang et al. (Wang et al., 2013), which was implemented as a Roddy Workflow (https://github.com…”
Andréjak, C., Almeida, D. V., Tyagi, S. K., Converse, P. J., Ammerman, N. C., & Grosset, J. H. E. (2015) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.04841-14 · Cited by 74 · see citing works
Environmental influences on clonal hematopoiesis
King, K. Y., Huang, Y., Nakada, D., & Goodell, M. A. (2019) · Experimental Hematology · doi:10.1016/j.exphem.2019.12.005 · Cited by 74 · see citing works
Self-citationGanuza, M., Hall, T., Finkelstein, D., Wang, Y., Chabot, A., Kang, G., Bi, W., Wu, G., & McKinney‐Freeman, S. (2019) · Blood · doi:10.1182/blood-2018-09-873059 · Cited by 71 · see citing works
Self-citationHaemopoietic stem cells are organised for use on the basis of their generation-age
Rosendaal, M., HODGSON, G. S., & Bradley, T. R. (1976) · Nature · doi:10.1038/264068a0 · Cited by 68 · cited 1× · see citing works
“In this context, our data support a clonal succession/generational age model (Kay, 1965; Rosendaal et al., 1976) in which individual HSCs will be sequentially activated to proliferate with each exposure to inflammation, resulting in functional ‘‘exhaustion’’ for these clones.”
Antigen presentation safeguards the integrity of the hematopoietic stem cell pool
Hernández-Malmierca, P., Vonficht, D., Schnell, A., Uckelmann, H., Bollhagen, A., Mahmoud, M., Landua, S.-L., van der Salm, E., Trautmann, C. L., Raffel, S., et al. (2022) · Cell Stem Cell · doi:10.1016/j.stem.2022.04.007 · Cited by 67 · see citing works
Self-citationStress and Non-Stress Roles of Inflammatory Signals during HSC Emergence and Maintenance
Clapes, T., Lefkopoulos, S., & Trompouki, E. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00487 · Cited by 59 · see citing works
Haetscher, N., Feuermann, Y., Wingert, S., Rehage, M., Thalheimer, F. B., Weiser, C., Bohnenberger, H., Jung, K., Schroeder, T., Serve, H. L., et al. (2015) · Nature Communications · doi:10.1038/ncomms9928 · Cited by 58 · see citing works
Self-citationMeacham, C. E., Jeffery, E. C., Burgess, R. J., Sivakumar, C. D., Arora, M. A., Stanley, A. M., Colby, E. M., Crane, G. M., Zhao, Z., & Morrison, S. J. (2022) · Nature Cell Biology · doi:10.1038/s41556-022-00909-9 · Cited by 52 · see citing works
Common Sources of Inflammation and Their Impact on Hematopoietic Stem Cell Biology
Hormaechea‐Agulla, D., Le, D. T., & King, K. Y. (2020) · Current Stem Cell Reports · doi:10.1007/s40778-020-00177-z · Cited by 46 · see citing works
Self-citationLoss of epigenetic polarity is a hallmark of hematopoietic stem cell aging
Mejía-Ramírez, E., Geiger, H., & Florian, M. C. (2020) · Human Molecular Genetics · doi:10.1093/hmg/ddaa189 · Cited by 24 · see citing works
Self-citationTakizawa, H., Fritsch, K., Kovtonyuk, L. V., Saito, Y., Yakkala, C., Jacobs, K., Ahuja, A. K., Lopes, M., Hausmann, A., Hardt, W., et al. (2020) · Cell stem cell · doi:10.1016/j.stem.2020.06.010 · Cited by 24 · see citing works
Bockamp, E., Antunes, C., Maringer, M., Heck, R., Presser, K., Beilke, S., Ohngemach, S., Alt, R., Cross, M. A., Sprengel, R., et al. (2006) · Blood · doi:10.1182/blood-2005-12-012104 · Cited by 19 · cited 1× · see citing works
“H2B-GFP and ScltTA mice have been previously described (Bockamp et al., 2006; Tumbar et al., 2004; Wilson et al., 2008).”
Conditionally pathogenic genetic variants of a hematopoietic disease–suppressing enhancer
Soukup, A. A., Matson, D. R., Liu, P., Johnson, K. D., & Bresnick, E. H. (2021) · Science Advances · doi:10.1126/sciadv.abk3521 · Cited by 14 · see citing works
Flagged first, then by citations
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 · see citing works
“Moreover, inflammatory death of internal cells due to exogenous factors such as infection also promotes the progression of inflammaging.(17,233) During aging, the imbalance between the increased production and decreased disposal via autophagy, mitophagy, and proteasome, stimulus the innate immune system and thereby tr…”
BackgroundChronic inflammation and the hallmarks of aging
Baechle, J. J., Chen, N., Makhijani, P., Winer, S., Furman, D., & Winer, D. A. (2023) · Molecular Metabolism · doi:10.1016/j.molmet.2023.101755 · Cited by 471 · see citing works
“[381] Bogeska R, Mikecin AM, Kaschutnig P, Fawaz M, Büchler-Schäff M, Le D,”
BackgroundThe decisive early phase of bone regeneration
Duda, G. N., Geißler, S., Checa, S., Tsitsilonis, S., Petersen, A., & Schmidt‐Bleek, K. (2023) · Nature Reviews Rheumatology · doi:10.1038/s41584-022-00887-0 · Cited by 417 · see citing works
Bao, H., Cao, J., Chen, M., Min, C., Chen, W., Chen, X., Chen, Y., Chen, Y., Chen, Y., Chen, Z., et al. (2023) · Science China Life Sciences · doi:10.1007/s11427-023-2305-0 · Cited by 389 · see citing works
Deep insight into cytokine storm: from pathogenesis to treatment
Nie, J., Zhou, L., Tian, W., Liu, X., Yang, L., Yang, X., Zhang, Y., Wei, S., Wang, D. W., & Wei, J. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02178-y · Cited by 224 · see citing works
Innate immune pathways and inflammation in hematopoietic aging, clonal hematopoiesis, and MDS
Trowbridge, J. J., & Starczynowski, D. T. (2021) · Journal of Experimental Medicine · doi:10.1084/jem.20201544 · Cited by 189 · see citing works
Blood-to-brain communication in aging and rejuvenation
Bieri, G., Schroer, A. B., & Villeda, S. A. (2023) · Nature Neuroscience · doi:10.1038/s41593-022-01238-8 · Cited by 156 · see citing works
Jakobsen, N. A., Turkalj, S., Zeng, A. G. X., Stoilova, B., Metzner, M., Rahmig, S., Nagree, M. S., Shah, S., Moore, R., Usukhbayar, B., et al. (2024) · Cell Stem Cell · doi:10.1016/j.stem.2024.05.010 · Cited by 130 · see citing works
Mi, B., Xiong, Y., Knoedler, S. A., Alfertshofer, M. G., Panayi, A. C., Wang, H., Lin, S., Li, G., & Liu, G. (2024) · Bone Research · doi:10.1038/s41413-024-00346-4 · Cited by 144 · see citing works
Stress, epigenetics, and aging: Unraveling the intricate crosstalk
Wu, Z., Qu, J. T., Zhang, W., & Liu, G. (2023) · Molecular Cell · doi:10.1016/j.molcel.2023.10.006 · Cited by 142 · see citing works
Hematopoietic stem cells through the ages: A lifetime of adaptation to organismal demands
Kasbekar, M., Mitchell, C. A., Proven, M. A., & Passegue, E. A. (2023) · Cell stem cell · doi:10.1016/j.stem.2023.09.013 · Cited by 122 · see citing works
Poscablo, D. M., Worthington, A. K., Smith‐Berdan, S., Rommel, M. G. E., Manso, B. A., Adili, R., Mok, L., Reggiardo, R. E., Cool, T., Mogharrab, R., et al. (2024) · Cell · doi:10.1016/j.cell.2024.04.018 · Cited by 117 · see citing works
HIV is associated with an increased risk of age-related clonal hematopoiesis among older adults
Dharan, N. J., Yeh, P., Bloch, M., Yeung, M. M., Baker, D., Guinto, J., Roth, N., Ftouni, S., Ognenovska, K., Smith, D., et al. (2021) · Nature Medicine · doi:10.1038/s41591-021-01357-y · Cited by 108 · see citing works
Epigenetic reprogramming as a key to reverse ageing and increase longevity
Pereira, B., Correia, F. P., Alves, I. A., Costa, M., Gameiro, M. D., Martins, A. P., & Saraiva, J. A. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102204 · Cited by 108 · see citing works
Chronic Stress and Autoimmunity: The Role of HPA Axis and Cortisol Dysregulation
Nunez, S. G., Rabelo, S. P., Subotic, N., Caruso, J. W., & Knezevic, N. N. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26209994 · Cited by 138 · see citing works
“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].”
Made to order: Emergency myelopoiesis and demand-adapted innate immune cell production
Swann, J. W., Olson, O., & Passegué, E. (2024) · Nature reviews. Immunology · doi:10.1038/s41577-024-00998-7 · Cited by 89 · see citing works
“proliferation and differentiation 74 , re-entry of HSCs into quiescence is a critical concluding event in EM pathway activation to prevent haematopoietic failure, as demonstrated by loss of the HSC compartment in mice lacking critical mediators of quiescence such as FOXO3A 75 or with compromised…”
Clonal hematopoiesis and inflammation – the perpetual cycle
Avagyan, S., & Zon, L. I. (2023) · Trends in Cell Biology · doi:10.1016/j.tcb.2022.12.001 · Cited by 79 · see citing works
Age-related bone diseases: Role of inflammaging
Bi, J., Zhang, C., Lu, C., Mo, C., Zeng, J., Yao, M., Jia, B., Liu, Z., Yuan, P., & Xu, S. (2024) · Journal of Autoimmunity · doi:10.1016/j.jaut.2024.103169 · Cited by 83 · see citing works
Hematopoietic stem cell aging and leukemia transformation
Díaz, P. A. C., Mistry, J. J., & Trowbridge, J. J. (2023) · Blood · doi:10.1182/blood.2022017933 · Cited by 78 · see citing works
“64 Increased levels of interleukin 1 β (IL-1 β ) produced by old and damaged endosteum 65 reduces HSC self-renewal 66 and increases myeloid cell proliferation.”
Clonal dynamics of haematopoiesis across the human lifespanPreprint
Mitchell, E., Chapman, M. S., Williams, N., Dawson, K. J., Mende, N., Calderbank, E. F., Jung, H., Mitchell, T. J., Coorens, T. H. H., Spencer, D. H., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.08.16.456475 · Cited by 74 · see citing works
Patrick, R., Naval-Sánchez, M., Deshpande, N., Huang, Y., Zhang, J., Chen, X., Yang, Y., Tiwari, K., Esmaeili, M., Tran, M., et al. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2024.06.006 · Cited by 73 · see citing works
Genetic engineering meets hematopoietic stem cell biology for next-generation gene therapy
Ferrari, S., Valeri, E., Conti, A., Scala, S., Aprile, A., Micco, R. D., Kajaste‐Rudnitski, A., Montini, E., Ferrari, G., Aiuti, A., et al. (2023) · Cell stem cell · doi:10.1016/j.stem.2023.04.014 · Cited by 71 · see citing works
Inflammation, Aging and Hematopoiesis: A Complex Relationship
Bousounis, P., Bergo, V., & Trompouki, E. (2021) · Cells · doi:10.3390/cells10061386 · Cited by 58 · see citing works
The role of the haematopoietic stem cell niche in development and ageing
Cain, T. L., Derecka, M., & McKinney‐Freeman, S. (2024) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-024-00770-8 · Cited by 59 · see citing works
“A recent study also showed that repeated inflammatory challenge mimicking viral infections leads to HSC attrition that resembles accelerated ageing 203 .”
Self-citationCCL2-mediated inflammatory pathogenesis underlies high myopia-related anxiety
Zhu, X., Meng, J., Han, C., Wu, Q., Du, Y., Qi, J., Wei, L., Li, H., He, W., Zhang, K., et al. (2023) · Cell Discovery · doi:10.1038/s41421-023-00588-2 · Cited by 52 · see citing works
Hematopoietic Stem Cells and the Immune System in Development and Aging
Shevyrev, D., Tereshchenko, V., Berezina, T. N., & Александрович, Р. С. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24065862 · Cited by 54 · see citing works
Ageing, immune fitness and cancer
Dolan, M., Libby, K. A., Ringel, A. E., van Galen, P., & McAllister, S. S. (2025) · Nature reviews. Cancer · doi:10.1038/s41568-025-00858-z · Cited by 50 · see citing works
“Mouse studies further show that both IFNα and IFNγ drive dormant HSCs into the cell cycle 77,78 , and repeated HSC activation leads to functional attrition and accelerated ageing phenotypes, characterized by increased myeloid differentiation and reduced clonal diversity 79 (Fig.”
Bone Marrow Immune Microenvironment in Myelodysplastic Syndromes
Kouroukli, O., Symeonidis, A. S., Foukas, P. G., Maragkou, M., & Kourea, E. P. (2022) · Cancers · doi:10.3390/cancers14225656 · Cited by 48 · see citing works
Bone marrow niches for hematopoietic stem cells: Life span dynamics and adaptation to acute stress
Hofmann, J., & Kokkaliaris, K. D. (2024) · Blood · doi:10.1182/blood.2023023788 · Cited by 45 · see citing works
Qi, L., Fang, X., Yan, J., Pan, C., Ge, W., Wang, J., Shen, S. G., Lin, K., & Zhang, L. (2023) · Bioactive Materials · doi:10.1016/j.bioactmat.2023.10.024 · Cited by 45 · see citing works
Mechanisms of hematopoietic clonal dominance in VEXAS syndrome
Molteni, R., Fiumara, M., Campochiaro, C., Alfieri, R. R., Pacini, G., Licari, E., Tomelleri, A., Diral, E., Varesi, A., Weber, A., et al. (2025) · Nature Medicine · doi:10.1038/s41591-025-03623-9 · Cited by 46 · see citing works
“Exposure to IL-1β or chronic inflammatory stimuli is known to prime primitive HSCs toward myelopoiesis, erode their self-renewing capacity and accelerate aging 70,84,85 .”
Genotoxic aldehyde stress prematurely ages hematopoietic stem cells in a p53-driven manner
Wang, M., Brandt, L. T. L., Wang, X., Russell, H., Mitchell, E., Kamimae-Lanning, A. N., Brown, J. M., Dingler, F. A., Garaycoechea, J. I., Isobe, T., et al. (2023) · Molecular Cell · doi:10.1016/j.molcel.2023.05.035 · Cited by 44 · see citing works
Liu, C., Liao, W., Chen, J., Yu, K., Wu, Y., Zhang, S., Chen, M., Chen, F., Wang, S., Cheng, T., et al. (2023) · Redox Biology · doi:10.1016/j.redox.2023.102661 · Cited by 41 · see citing works
Stem-Cell Aging and Pathways to Precancer Evolution
Jamieson, C. H. M., & Weissman, I. L. (2023) · New England Journal of Medicine · doi:10.1056/nejmra2304431 · Cited by 40 · see citing works
Unraveling immunosenescence in sepsis: from cellular mechanisms to therapeutics
Wang, Y., Zhang, H., & Miao, C. (2025) · Cell Death and Disease · doi:10.1038/s41419-025-07714-w · Cited by 41 · see citing works
“Critically, short-term in fl ammatory stimuli are suf fi cient to suppress hematopoietic function, which is different from HSCs senescence induced by persistent strong in fl ammatory stimulation or aging-related chronic low-grade in fl ammation [11].”
Chen, D.-W., Fan, J.-M., Schrey, J. M., Mitchell, D. V., Jung, S. K., Hurwitz, S. N., Perez, E., Muraro, M. J., Carroll, M. P., Taylor, D. M., et al. (2023) · bioRxiv · doi:10.1038/s41375-024-02136-7 · Cited by 32 · see citing works
“Due to space constraints, please refer to the “ Supplementary – Expanded Methods ” section for extensive methods description.”
Forged in the fire: Lasting impacts of inflammation on hematopoietic progenitors
Cao, R., Thatavarty, A., & King, K. Y. (2024) · Experimental Hematology · doi:10.1016/j.exphem.2024.104215 · Cited by 34 · see citing works
“This loss of function occurs as a natural phenotype of aging but has been found to be exacerbated by repeated exposures to inflammatory stimuli 24 .”
Self-citationYoung, K. A., Hosseini, M., Mistry, J. J., Morganti, C., Mills, T., Cai, X., James, B., Nye, G. J., Fournier, N. R., Voisin, V., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-57238-2 · Cited by 36 · see citing works
Aged hematopoietic stem cells entrap regulatory T cells to create a prosurvival microenvironment
Liao, W., Liu, C., Yang, K., Chen, J., Wu, Y., Zhang, S., Yu, K., Wang, L., Li, R., Chen, M., et al. (2023) · Cellular and Molecular Immunology · doi:10.1038/s41423-023-01072-3 · Cited by 32 · see citing works
Yang, Y., Peng, H., Wang, J., & Li, F. (2024) · Experimental Hematology and Oncology · doi:10.1186/s40164-024-00573-9 · Cited by 32 · see citing works
IRF1 regulates self-renewal and stress responsiveness to support hematopoietic stem cell maintenance
Nilsson, A. R., Xian, H., Shalapour, S., Cammenga, J., & Karin, M. (2023) · Science Advances · doi:10.1126/sciadv.adg5391 · Cited by 31 · see citing works
Immune aging and infectious diseases
Chen, R., Zou, J., Chen, J., Wang, L., Kang, R., & Tang, D. (2024) · Chinese Medical Journal · doi:10.1097/cm9.0000000000003410 · Cited by 33 · see citing works
“[ 87 ] Therefore, inflammaging impairs self-renewal activity and accelerates the aging of HSCs. Aged HSCs tend to differentiate more toward myeloid lineages, resulting in fewer lymphocyte precursors, specifically affecting T-and B-cell production [ Figure 3C ].”
Inflammageing and clonal haematopoiesis interplay and their impact on human disease
Hajishengallis, G., & Chavakis, T. (2026) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-025-00936-y · Cited by 36 · see citing works
Fate of Hematopoiesis During Aging. What Do We Really Know, and What are its Implications?
Broxmeyer, H. E., Liu, Y., Kapur, R., Orschell, C. M., Aljoufi, A., Ropa, J. P., Trinh, T. L. P., Burns, S. S., & Capitano, M. L. (2020) · Stem Cell Reviews and Reports · doi:10.1007/s12015-020-10065-y · Cited by 30 · see citing works
Risk factors for clonal hematopoiesis of indeterminate potential and mosaic chromosomal alterations
Jakubek, Y. A., Reiner, A. P., & Honigberg, M. C. (2022) · Translational research · doi:10.1016/j.trsl.2022.11.009 · Cited by 30 · see citing works
Influenza A virus infection instructs hematopoiesis to megakaryocyte-lineage output.
Rommel, M. G. E., Walz, L., Fotopoulou, F., Kohlscheen, S., Schenk, F., Miskey, C., Botezatu, L., Krebs, Y., Voelker, I., Wittwer, K., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111447 · Cited by 27 · see citing works
Self-citationNasiri, K., Mohammadzadehsaliani, S., Kheradjoo, H., Shabestari, A. M., Eshaghizadeh, P., Pakmehr, A., Alsaffar, M. F., Al-Naqeeb, B. Z. T., Yasamineh, S., & Gholizadeh, O. (2023) · Cell Communication and Signaling · doi:10.1186/s12964-023-01122-3 · Cited by 28 · see citing works
“It is uncertain whether the functional impairment of HSCs caused by these stresses persists beyond the period of inflammatory exposure [3].”
BackgroundThe biology of hematopoietic stem cells and its clinical implications
Skulimowska, I., Sośniak, J., Gońka, M., Szade, A., Józkowicz, A., & Szade, K. (2021) · FEBS Journal · doi:10.1111/febs.16192 · Cited by 26 · see citing works
DRAG in situ barcoding reveals an increased number of HSPCs contributing to myelopoiesis with age
Urbanus, J. H. M., Cosgrove, J., Beltman, J. B., Elhanati, Y., Moral, R. D. A., Conrad, C., van Heijst, J. W. J., Tubeuf, E., Velds, A., Kok, L., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-37167-8 · Cited by 25 · see citing works
Müller, L., & Benedetto, S. D. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1393324 · Cited by 25 · see citing works
Aging microenvironment in osteoarthritis focusing on early-stage alterations and targeted therapies
Dang, Y., Liu, Y., Zhang, B., & Zhang, X. (2025) · Bone Research · doi:10.1038/s41413-025-00465-6 · Cited by 27 · see citing works
“111 These results implied that the interaction of immune response and stem cells could contribute to OA progressive cartilage degeneration, indicating that early intervention of immune homeostatic imbalance is the window of opportunity for OA treatment.”
Munz, C. M., Dressel, N., Chen, M., Grinenko, T., Roers, A., & Gerbaulet, A. (2023) · Blood · doi:10.1182/blood.2022018996 · Cited by 25 · see citing works
Identification of a human hematopoietic stem cell subset that retains memory of inflammatory stressPreprint
Zeng, A. G. X., Nagree, M. S., Jakobsen, N. A., Shah, S., Murison, A., Cheong, J.-G., Turkalj, S., Lim, I., Jin, L.-Q., Araújo, J., et al. (2023) · bioRxiv · doi:10.1101/2023.09.11.557271 · Cited by 15 · see citing works
Lin, H.-L., Sheng, W., Sato, K., Zhang, Y. Q., He, B. T., Xu, J., Nakazawa, T., Qin, Y., & Zhang, H. (2024) · Cell Death Discovery · doi:10.1038/s41420-024-01900-z · Cited by 24 · see citing works
Ki, M., Kim, D. H., Abdelhamid, M. A. A., & Pack, S. P. (2025) · Biosensors · doi:10.3390/bios15110737 · Cited by 29 · see citing works
How age affects human hematopoietic stem and progenitor cells and the strategies to mitigate aging
Li, X., Wang, J., Hu, L., & Cheng, T. (2025) · Experimental Hematology · doi:10.1016/j.exphem.2025.104711 · Cited by 22 · see citing works
Chronic inflammation decreases HSC fitness by activating the druggable Jak/Stat3 signaling pathway
Grusanovic, S., Daněk, P., Kuzmina, M., Adamcova, M. K., Burócziová, M., Mikyšková, R., Vanickova, K., Kosanovic, S., Pokorna, J., Reiniš, M., et al. (2022) · EMBO Reports · doi:10.15252/embr.202254729 · Cited by 21 · see citing works
“…mice challenged with pathogens, polyinosinic:polycytidylic acid (pI:pC) or lipopolysaccharide (LPS) exhibited functional defects in HSCs (Baldridge et al , 2010; Esplin et al , 2011; Zhao et al , 2013; Walter et al , 2015; Matatall et al , 2016; Isringhausen et al , 2021; Bogeska et al , 2022).”
Rettkowski, J., Romero-Mulero, M. C., Singh, I., Wadle, C., Wrobel, J., Chiang, D., Hoppe, N., Mess, J., Schönberger, K., Lalioti, M., et al. (2025) · Nature Cell Biology · doi:10.1038/s41556-025-01639-4 · Cited by 24 · see citing works
Haematopoietic ageing in health and lifespan
Andersson, R., Mejía-Ramírez, E., & Florian, M. C. (2025) · Nature Cell Biology · doi:10.1038/s41556-025-01739-1 · Cited by 24 · see citing works
“…are at the level of DNA damage 20–22 , epigenetics (DNA hypermethylation and histone post-translational modifications 23–27 , H4K16ac polarity 28–31 , increased overall chromatin accessibility 17,32 ), metabolism (high levels of reactive oxygen species (ROS) 33 , mitochondrial stress 34 ),…”
Self-citationReversing lysosomal dysfunction restores youthful state in aged hematopoietic stem cells
Arif, T., Qiu, J., Khademian, H., Lohithakshan, A., Menon, A., Menon, V., Slavinsky, M., Batignes, M., Miao, L., Sebra, R., et al. (2025) · Cell stem cell · doi:10.1016/j.stem.2025.10.012 · Cited by 24 · see citing works
Avogaro, A., de Kreutzenberg, S. V., Morieri, M. L., Fadini, G. P., & Prato, S. D. (2022) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(22)00247-9 · Cited by 21 · see citing works
New insight into the causes, consequences, and correction of hematopoietic stem cell aging
Mansell, E., Lin, D. S. Y., Loughran, S. J., Milsom, M. D., & Trowbridge, J. J. (2023) · Experimental Hematology · doi:10.1016/j.exphem.2023.07.002 · Cited by 21 · see citing works
Self-citationSuppression of thrombospondin-1–mediated inflammaging prolongs hematopoietic health span
Ramalingam, P., Gutkin, M. C., Poulos, M. G., Winiarski, A., Smith, A., Carter, C., Doughty, C., Tillery, T., Redmond, D., Freire, A. G., et al. (2025) · Science Immunology · doi:10.1126/sciimmunol.ads1556 · Cited by 17 · see citing works
Role of chemokines in aging and age-related diseases
Chaudhary, J. K., Danga, A. K., Kumari, A., Bhardwaj, A., & Rath, P. C. (2024) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2024.112009 · Cited by 20 · see citing works
Mou, R., Ma, J., Ju, X., Wu, Y., Chen, Q., Li, J., Shang, T., Chen, S., Yang, Y., Li, Y., et al. (2024) · Cell Stem Cell · doi:10.1016/j.stem.2024.09.018 · Cited by 20 · see citing works
Salminen, A., Kaarniranta, K., & Kauppinen, A. (2025) · Biogerontology · doi:10.1007/s10522-025-10353-5 · Cited by 19 · see citing works
“One possible source could be many pro-inflammatory SASP factors which are released from senescent cells present in aged peripheral tissues (Fujino et al. 2022; Bogeska et al. 2022).”
Chen, Z., Mao, Z., Tang, W., Shi, Y., Liu, J., & You, Y. (2025) · Translational Neurodegeneration · doi:10.1186/s40035-025-00517-1 · Cited by 21 · see citing works
“5) [79, 158, 163–165].”
Zhao, H., & Deininger, M. W. (2023) · Blood · doi:10.1182/blood.2022017152 · Cited by 21 · see citing works
Bloom, M., Oak, N., Baskin-Doerfler, R., Feng, R., Iacobucci, I., Baviskar, P. S., Zhao, X., Stroh, A. N., Li, C., Ozark, P. A., et al. (2023) · Blood Advances · doi:10.1182/bloodadvances.2022009313 · Cited by 19 · see citing works
“33 For example, recent work has shown that in fl ammatory exposures create long-term impairment of HSC self-renewal and accelerate hematopoietic aging, 37 and reduce the fi tness of B-cell progenitors, creating an environment that selects for cells harboring oncogenic mutations.”
Self-citationLinking cell cycle to hematopoietic stem cell fate decisions
Treichel, S., & Filippi, M. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1231735 · Cited by 19 · see citing works
“Amodel where HSCs replicate into gradually less functional progeny has been shown to occur under mild inflammatory conditions (Qiu et al., 2014; Bernitz et al., 2016; Bogeska et al., 2022).”
BackgroundBeyond “to divide or not to divide”: Kinetics matters in hematopoietic stem cells
Johnson, C., Belluschi, S., & Laurenti, E. (2020) · Experimental Hematology · doi:10.1016/j.exphem.2020.11.003 · Cited by 17 · see citing works
Temporal dynamics of TNF-mediated changes in hematopoietic stem cell function and recovery
Nilsson, A. R., Hidalgo, I., Bryder, D., & Pronk, C. J. (2023) · iScience · doi:10.1016/j.isci.2023.106341 · Cited by 17 · see citing works
“Similarly, chronic polyinosinic:polycytidylic acid (pI:pC) stimulation reduced the repopulating capacity of HSCs, albeit without exhaustion of HSCs in the primary hosts.(12,13) By contrast, the impaired HSC repopulation ability after chronic stimulation with IL-1 could be fully restored upon removal of the stimulus an…”
BackgroundInflammation in myelodysplastic syndrome pathogenesis
Rodríguez‐Sevilla, J. J., & Colla, S. (2024) · Seminars in Hematology · doi:10.1053/j.seminhematol.2024.09.005 · Cited by 18 · see citing works
Fotopoulou, F., Rodriguez-Correa, E., Dussiau, C., & Milsom, M. D. (2024) · Experimental Hematology · doi:10.1016/j.exphem.2024.104698 · Cited by 17 · see citing works
Self-citationLandsberger, T., Amit, I., & Alon, U. S. (2023) · GeroScience · doi:10.1007/s11357-023-00915-1 · Cited by 16 · see citing works
Lin, D. S. Y., & Trumpp, A. (2023) · Cells and Development · doi:10.1016/j.cdev.2023.203843 · Cited by 14 · see citing works
The Quest for Eternal Youth: Hallmarks of Aging and Rejuvenating Therapeutic Strategies
Nunkoo, V. S., Cristian, A., Jurcău, A., Diaconu, R. G., & Jurcău, M. C. (2024) · Biomedicines · doi:10.3390/biomedicines12112540 · Cited by 15 · see citing works
Bone marrow niches for hematopoietic stem cells in homeostasis and aging
Nakatani, T., & Nagasawa, T. (2025) · Experimental Hematology · doi:10.1016/j.exphem.2025.104749 · Cited by 14 · see citing works
Wang, J., Zhang, L.-L., Cui, X., Xu, X., Guo, R., Li, K., Zhang, L., Xu, B., Jiang, C.-Z., & Yu, Y. (2025) · Science immunology · doi:10.1126/sciimmunol.adr2041 · Cited by 14 · see citing works
Filippi, M. (2021) · Experimental Hematology · doi:10.1016/j.exphem.2021.01.006 · Cited by 14 · see citing works
Human haematopoietic stem cells remember inflammatory stress
Zeng, A. G. X., Nagree, M. S., Jakobsen, N. A., Shah, S., Varesi, A., Kang, J. R. W., Murison, A., Cheong, J.-G., Turkalj, S., Zhang, X., et al. (2026) · Nature · doi:10.1038/s41586-026-10522-7 · Cited by 10 · see citing works
“Finally, as HSC-iM enrichment can reflect the systemic level of inflammation in unhealthy individuals, some of the disease correlations attributed to CH status in current literature may potentially reflect survivorship bias of an earlier HSC-iM-driven inflammatory state 1,4 .”
Cellular stress and epigenetic regulation in adult stem cells
Llewellyn, J., Baratam, R., Culig, L., & Beerman, I. (2024) · Life Science Alliance · doi:10.26508/lsa.202302083 · Cited by 13 · see citing works
“In another study, fi ndings reveal that such impairments can be irreversible, with no recovery observed even after a year (108).”
BackgroundHow stem cells respond to infection, inflammation and ageing
Poirier, E. Z. (2025) · Nature reviews. Immunology · doi:10.1038/s41577-025-01203-z · Cited by 13 · see citing works
“3).”
Hu, H., Mei, J., Mei, L., Wu, X., Lin, H., & Chen, G. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.996863 · Cited by 13 · see citing works
“Recently, it has been found that long-term stimulation by chronic inflammation causes a significant decrease in the proliferative capacity of hematopoietic stem cells, the origin of immune cells, resulting in accumulative and irreversible functional damage and long-term suppressive effects on hematopoiesis, further co…”
BackgroundGuan, D., Yang, Y., Pang, M., Liu, X., Li, Y., Huang, P., Shang, H., Wei, H., & Ye, Z. (2023) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-023-04732-0 · Cited by 13 · see citing works
“Inflammation is a key insult driving HSPC injury and inhibition of systemic inflammation confer protection against radiation damage [42, 43].”
Single-cell time series analysis reveals the dynamics of HSPC response to inflammation
Bouman, B. J., Demerdash, Y., Sood, S., Grünschläger, F., Pilz, F., Itani, A. R., Kuck, A., Marot-Lassauzaie, V., Haas, S. F., Haghverdi, L., et al. (2023) · Life Science Alliance · doi:10.26508/lsa.202302309 · Cited by 12 · see citing works
“This indicates irreversible changes that leave a mark in the activated cells (Bogeska et al, 2022).”
BackgroundSelf-citationIn vivo models of subclonal oncogenesis and dependency in hematopoietic malignancy
Bowman, R. L., Dunbar, A. J., Mishra, T., Xiao, W., Waarts, M., Maestre, I. F., Eisman, S. E., Cai, L., Mowla, S., Shah, N., et al. (2024) · Cancer Cell · doi:10.1016/j.ccell.2024.10.009 · Cited by 14 · see citing works
Hematopoietic stem cell a reservoir of innate immune memory
Ruffinatto, L., Groult, Y., Iacono, J., Sarrazin, S., & de Laval, B. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1491729 · Cited by 14 · see citing works
The genetic determinants of recurrent somatic mutations in 43,693 blood genomes
Weinstock, J., Laurie, C., Broome, J., Taylor, K., Guo, X.-Q., Shuldiner, A., O'Connell, J., Lewis, J., Boerwinkle, E., Barnes, K., et al. (2023) · Science Advances · doi:10.1126/sciadv.abm4945 · Cited by 12 · see citing works
Li, J., Xiang, Q., Xia, T., Meng, H., & Liu, X. (2023) · Nano Today · doi:10.1016/j.nantod.2023.101978 · Cited by 12 · see citing works
Nunes, J. J., & Loeffler, D. (2024) · Frontiers in Hematology · doi:10.3389/frhem.2024.1373554 · Cited by 13 · see citing works
Maintenance of hematopoietic stem cells by tyrosine-unphosphorylated STAT5 and JAK inhibition
Williams, M., Wang, X., Bastos, H. P., Grondys-Kotarba, G., Johnson, C., Mende, N., Calderbank, E. F., Wantoch, M., Park, H. J., Wu, Q., et al. (2024) · Blood Advances · doi:10.1182/bloodadvances.2024014046 · Cited by 13 · see citing works
Cui, X., Dong, Y., Zhan, Q., Huang, Y., Zhu, Q., Zhang, Z., Yang, G., Wang, L., Shen, S., Zhao, J., et al. (2024) · Science China Life Sciences · doi:10.1007/s11427-024-2754-9 · Cited by 14 · see citing works
“A recent work shows that inflammation insult, even in the early lifetime, causes permanent impairment and premature aging of HSCs (Bogeska et al., 2022).”
InfluentialVEXAS: A review of current understandings and emerging treatment strategies
Holden, R., Jeelall, Y., McLean‐Tooke, A. P., Pathmanathan, K., & Nolan, D. A. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1644404 · Cited by 11 · see citing works
Restoring resident tissue macrophages to combat aging and cancer
Park, M. D., Yatim, N., Zhang, J., Cho, B. A., Yoo, S., Schaefer, M. M., Chowell, D., Puleston, D. J., & Mérad, M. (2025) · Nature Aging · doi:10.1038/s43587-025-00898-y · Cited by 12 · see citing works
Kottmann, V., Nienhaus, M., Drees, P., Gercek, E., & Ritz, U. (2026) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2026.189551 · Cited by 14 · see citing works
From complexity to clarity: aging bone marrow niche in bone and blood regeneration and malignancy
Roy, N., Liu, H., Horenberg, A. L., Pathak, A. P., Chen, J., Ramasamy, S. K., Cohen-Solal, M. E., Bözec, A., Grayson, W. L., & Kusumbe, A. P. (2026) · Bone Research · doi:10.1038/s41413-026-00543-3 · Cited by 11 · see citing works
Association between anemia and serum Klotho in middle-aged and older adults
An, C., Chen, X., & Zheng, D. (2023) · BMC Nephrology · doi:10.1186/s12882-023-03081-w · Cited by 11 · see citing works
“Inflammatory stimulation of mice in early to middle age results in eventual peripheral haemocytopenia, bone marrow cytopenia, and build-up of bone marrow adipocytes, which together constitute typical features of hematopoiesis in elderly humans [16].”
BackgroundJakobsen, N. A., Turkalj, S., Zeng, A. G. X., Stoilova, B., Metzner, M., Nagree, M. S., Shah, S., Moore, R., Usukhbayar, B., Salazar, M. A., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.09.12.557322 · Cited by 11 · see citing works
Andrzejczak, K., Sternak, A., Witkowski, W., & Ponikowska, M. (2025) · Cells · doi:10.3390/cells14181442 · Cited by 10 · see citing works
“Prolonged exposure to chronic inflammation exacerbates HSC senescence, further impairing their function [12,13].”
- 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 · 2021: 8 · 2020: 3
- 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
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
