Aging-induced IL27Ra signaling impairs hematopoietic stem cells
Open accessAbstract
Hematopoietic stem cell (HSC) aging correlates with an increasing risk of myeloproliferative disease and immunosenescence. In this study, we show that aging-related inflammation promotes HSC aging through tumor necrosis factor-α (TNF-α)→ERK→ETS1→interleukin27Ra (IL27Ra) pathway. TNF-α, a well-known biomarker of inflammation, increases during aging and induces the expression of IL27Ra on HSCs via ERK-ETS1 signaling. Deletion of IL27Ra rescues the functional decline and myeloid bias of HSCs and also reverses the inhibitory effect of TNF-α on HSCs. Aged IL27Ra−/− mice had a reduced proportion of myeloid-biased HSCs and did not display the biased myeloid differentiation that occurs in aged wild-type mice. IL27Ra+ HSCs exhibit impaired reconstitution capacity and myeloid-bias compared with IL27Ra− HSCs and serve as a myeloid-recovery pool upon inflammatory insult. Inflammation-related genes were enriched in IL27Ra+ HSCs and this enrichment increases with aging. Our study demonstrates that age-induced IL27Ra signaling impairs HSCs and raises the possibility that interfering with IL27Ra signaling can counter the physiologically deleterious effect of aging on hematopoietic capacity.
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Inflammatory cytokines, including TNF, TGF1β, IL-6 and IL-1β, have been found to be upregulated in aged bone marrow (HSC niche).
“Inflammatory cytokines, including TNF76, transforming growth factor-β1 (TGF1β)77, IL-6 (REF.78) and IL-1β (REF.79), have also been found to be upregulated in aged bone marrow (HSC niche).”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [76]
In the bone marrow, TNF induces the expression of IL-27 receptor, and ablation of IL-27 receptor blunts the negative impact of ageing on HSCs.
“In the bone marrow, TNF (likely produced by niche cells) induces the expression of IL-27 receptor, and ablation of IL-27 receptor blunts the negative impact of ageing on HSCs76.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [76]
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YTHDF3 modulates hematopoietic stem cells by recognizing RNA m6A modification on Ccnd1
Zhang, X., Cong, T., Wei, L., Zhong, B., Wang, X., Sun, J., Wang, S., Xu, M. M., Zhu, P., Jiang, H., et al. (2022) · Haematologica · doi:10.3324/haematol.2021.279739 · Cited by 29 · see citing works
“To further investigate the transcriptional difference be-tween Ythdf3 -/- and WT HSC, we performed RNA sequencing for those cells (Figure 2H).”
InfluentialSelf-citationGong, H., Ma, S., Chen, J., Yang, B., Liu, S., Liu, X., Han, J., Wu, X., Lei, L., Yin, Z., et al. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01147-z · Cited by 28 · see citing works
“IL-27Rα is constitutively expressed among a range of cell types including T cells, B cells, intestinal epithelial cells as well as hematopoietic stem cells.(9,10) Engagement of IL-27 and IL27 receptor transduces cellular signals via JAK1/2 and STAT1/3 pathways.”
BackgroundLifelong partners: Gut microbiota-immune cell interactions from infancy to old age
Brown, J. A., Bashir, H., & Zeng, M. Y. (2025) · Mucosal Immunology · doi:10.1016/j.mucimm.2025.01.006 · Cited by 30 · see citing works
TNFα/TNFR1 signal induces excessive senescence of decidua stromal cells in recurrent pregnancy loss
Zeng, S., Liang, Y., Lai, S., Bi, S., Huang, L., Li, Y., Deng, W., Xu, P., Liu, M., Xiong, Z., et al. (2022) · Journal of Reproductive Immunology · doi:10.1016/j.jri.2022.103776 · Cited by 26 · see citing works
Self-citationThe dual role of cellular senescence in human tumor progression and therapy
Ma, L., Yu, J., Fu, Y., He, X., Ge, S., Jia, R., Zhuang, A., Yang, Z. H., & Fan, X. (2024) · MedComm · doi:10.1002/mco2.695 · Cited by 29 · see citing works
“165 Similarly, some researchers have studied the key factor involved in bone marrow cancer, myeloid erythroid transformation-related gene 3, the level of which determines the balance between the myeloid system and the lymphoid system in bone marrow stem cells.”
BackgroundHow 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
Self-citationZhou, L., Zhong, Y., Wang, F., Guo, Y., Mao, R., Xie, H., Zhang, Y., & Li, J. (2024) · International Journal of Biological Sciences · doi:10.7150/ijbs.90459 · Cited by 22 · see citing works
“Moreover, signaling axis involved in the aging process of hematopoietic stem cells (HSC) [52].”
BackgroundCiaglia, E., Lopardo, V., Montella, F., Carrizzo, A., Pietro, P. D., Malavolta, M., Giacconi, R., Orlando, F., Cattaneo, M., Madeddu, P. R., et al. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-04535-z · Cited by 23 · see citing works
“These cytokines belong to well-known pathways which, when active in aging, mediate aberrancy in hematopoietic stem cells HSC compartment, reduced reconstitution potential, impaired selfrenewal, and a pro-inflammatory phenotype [49].”
BackgroundZhu, X., Liu, J., Pan, H., Geng, Z., Huang, W. J., Liu, T., & Zhang, B. (2021) · International Journal of Medical Sciences · doi:10.7150/ijms.61975 · Cited by 21 · see citing works
“A growing number of studies have pointed out that cytokines, especially inflammatory factors, can induce ovarian tissue or follicle aging and death [26-29].”
BackgroundSobrino, S., Joseph, L., Magrin, E., Chalumeau, A., Hebert, N., Corsia, A., Denis, A., Roudaut, C., Aussel, C., Leblanc, O., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-58321-4 · Cited by 22 · see citing works
“Chronic in fl ammation can lead to premature aging of HSCs, which are biased towards the megakaryocytic or myeloid lineages 33,34,39 .”
Tissue mosaicism following stem cell aging: blood as an exemplar
Kapadia, C. D., & Goodell, M. A. (2024) · Nature Aging · doi:10.1038/s43587-024-00589-0 · Cited by 18 · see citing works
Function of hematopoiesis and bone marrow niche in inflammation and non-hematopoietic diseases
Wang, Y., Deng, Z., Li, Y.-Y., Bai, K., Ma, J., Liu, Y., & Chen, Q. (2025) · Life Medicine · doi:10.1093/lifemedi/lnaf015 · Cited by 17 · see citing works
“Nevertheless, the continued presence of TNF α signaling helps to maintain HSC function, although this is accompanied by an increase in myeloid differentiation and a reduction in lymphoid output [156].”
Inflammation and hematopoietic stem cells aging
He, H., & Wang, J. (2020) · Blood Science · doi:10.1097/bs9.0000000000000063 · Cited by 16 · see citing works
“They show that aging-related inflammation promotes HSC aging via a TNFa→ERK→ETS1→IL27Ra pathway.(11) IL-27 is a cytokine composed of EBI3-P28 heterodimer.”
BackgroundSelf-citationThe immunosenescence clock: A new method for evaluating biological age and predicting mortality risk
Li, S., Wang, K., Wu, J., & Zhu, Y. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102653 · Cited by 16 · see citing works
“Another example is that in aged hematopoietic stem cell (HSC) niches, inflammatory cytokines, including TNF-α and TGF-β , are also upregulated (He et al., 2020, Valletta et al., 2020).”
Li, J., Wang, C., Liu, J., Yu, Y., Liu, Y., Peng, Q., Liu, H., & Guan, X. (2021) · Molecular Biology Reports · doi:10.1007/s11033-021-06370-5 · Cited by 12 · see citing works
The dichotomic role of cytokines in aging
Silva, R. C. M. C. (2024) · Biogerontology · doi:10.1007/s10522-024-10152-4 · Cited by 14 · see citing works
“For example, TNF-induced IL-27 receptor (IL-27-Ra) is involved in the impaired reconstitution capacity and myeloid bias of aged hematopoietic stem cells (HSCs) in the presence of IL-27 (He et al. 2020).”
He, H., Wang, Y., & Wang, J. (2020) · Blood Science · doi:10.1097/bs9.0000000000000057 · Cited by 12 · see citing works
Self-citationAging-induced MCPH1 translocation activates necroptosis and impairs hematopoietic stem cell function
He, H., Wang, Y., Tang, B., Dong, Q., Wu, C., Sun, W., & Wang, J. (2024) · Nature Aging · doi:10.1038/s43587-024-00609-z · Cited by 11 · see citing works
Self-citationLiang, H., Ao, Y., Li, W., Liang, K., Tang, B., Li, J., Wang, J., Zhu, X., & Du, Y. (2022) · Bioactive Materials · doi:10.1016/j.bioactmat.2022.10.015 · Cited by 11 · see citing works
“1) mice (12 week-old) BM were isolated by BD Influx (BD Biosciences) as previously described [32].”
MethodSelf-citationAging-induced pseudouridine synthase 10 impairs hematopoietic stem cells
Wang, Y., Zhang, Z., He, H., Song, J., Cui, Y., Chen, Y., Zhuang, Y., Zhang, X., Li, M., Zhang, X., et al. (2023) · Haematologica · doi:10.3324/haematol.2022.282211 · Cited by 11 · see citing works
“3,4 Although previous studies have identi fi ed various molecular signaling pathways promoting HSC aging, 5-8 the exact molecular mechanism is still not fully understood.”
Self-citationMicrobiota Signals Suppress B Lymphopoiesis With Aging in Mice
Krambs, J. R., Monlish, D. A., Gao, F., Schuettpelz, L. G., & Link, D. C. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.767267 · Cited by 11 · see citing works
“This is relevant to aging, since chronic stimulation with IL1-b results in reduced HSC self-renewal and enhanced myeloid differentiation (21), and TNF-a signaling has been implicated in the reduced proliferation of aged pro-B cells and myeloid skewing of HSCs (22, 23).”
BackgroundAMPK/Sirt1-mediated inflammation is positively correlated with myocardial fibrosis during ageing
Song, Y., Zhang, Y., Zhang, X., Hu, S., Wang, J., Deng, G., & Zhou, Z. (2022) · Acta cardiologica. Supplementum · doi:10.1080/00015385.2022.2119667 · Cited by 10 · see citing works
“significantly during the ageing process [42,43].”
Self-citationDeGregori, J. V. (2020) · Blood · doi:10.1182/blood.2020006070 · Cited by 10 · see citing works
Aberrant engagement of P-selectin drives hematopoietic stem cell aging in mice
Yang, D., Skinder, N., Kao, Y.-R., Chen, J., Thiruthuvanathan, V. J., Svendsen, A. F., Zhang, C., Dethmers-Ausema, B., Weersing, E., Maryanovich, M., et al. (2025) · Nature Aging · doi:10.1038/s43587-025-00880-8 · Cited by 8 · see citing works
“Many inflammatory signals are elevated in aged BM 18,23,24,47,48,57 and some of these can induce Selp (and other aging genes).”
Liu, Z., Guo, X., Zhang, W., Wang, J., Zhang, L., Jing, J., Lin, H., & Gao, A. (2023) · Food and Chemical Toxicology · doi:10.1016/j.fct.2023.114030 · Cited by 7 · see citing works
Self-citationMetabolic regulation of aged hematopoietic stem cells: key players and mechanisms
Karimnia, N., Harris, J., Heazlewood, S. Y., Cao, B., & Nilsson, S. K. (2023) · Experimental Hematology · doi:10.1016/j.exphem.2023.09.006 · Cited by 7 · see citing works
Hematopoietic aging: Cellular, molecular, and related mechanisms
Ye, L., Tian, C., Li, Y., Pan, H., Hu, J., Shu, L., & Pan, X. (2023) · Chinese Medical Journal · doi:10.1097/cm9.0000000000002871 · Cited by 7 · see citing works
“[62] IGF2 is a cytokine that is positively related to hematopoietic aging and activates osteoblast differentiation; p16Ink4a is a negative regulator that participates in the apoptosis of HSCs mediated by the mTORC2-Akt signalling pathway to balance HSC output.”
BackgroundWang, Y., Song, Z., Geng, Y., Gao, L., Xu, L., Tang, G., Ni, X., Chen, L., Chen, J., Wang, T., et al. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.987965 · Cited by 7 · see citing works
“Age, median (range) 48 (12-64) 36 (17-66) 0.”
BackgroundInfluentialImmunotherapies for Aging and Age-Related Diseases: Advances, Pitfalls, and Prospects
Yang, M., Wu, S., Zhang, J., Lu, L., Deng, D., Xia, Q., Lovell, J. F., Shi, X., & Jin, H. (2025) · Research · doi:10.34133/research.0866 · Cited by 6 · see citing works
“Wang et al. [ 38 ] discovered that tumor necrosis factor-α (TNF-α ) activates extracellular signal–regulated kinase (ERK)–erythroblast transformation specific proto-oncogene 1 (ETS1) signaling pathway in HSCs of old mice, resulting in high expression of IL-27Ra, and thereby skewing these IL-27Ra +…”
Yang, Y., Lai, H., Liao, C., Chen, H., Jiang, X., Lin, C., He, L., Tu, H., & Jian, L. I. (2025) · BMC Geriatrics · doi:10.1186/s12877-025-06353-2 · Cited by 7 · see citing works
“Consequently, this establishes an adverse milieu characterized by excessive HSC proliferation, loss of pluripotency, and immune system depletion, thereby elevating the risk of anemia [21–27].”
GATA2 decommissioning of enhancers: A mechanism to constrain inflammatory signaling
Jung, M. M., Tran, V. L., Xiong, Y., Johnson, K. D., Katsumura, K. R., Liu, P., & Bresnick, E. H. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.116344 · Cited by 6 · see citing works
“75 As GATA2-PU.1 antagonism repressed Il6st enhancers to restrict IL-6 and IL-27 signaling, GED may have broader implications for immunopathology.”
Hematopoietic Stem Cell Aging: Mechanisms, Microenvironment Influences, and Rejuvenation Strategies
Cui, J., Li, X., Liu, B., Dong, C., & Chang, Y. (2025) · Bioengineering · doi:10.3390/bioengineering12111166 · Cited by 6 · see citing works
“He et al. demonstrated that the TNF-α → ERK → ETS1 → IL-27Ra signaling axis mediates pro-inflammatory responses that contribute to HSC aging by reducing self-renewal capacity and promoting a bias toward myeloid differentiation [48].”
InfluentialSelf-citationZheng, Y., Peng, L., He, Z., Zou, Z., Li, F., Huang, C., & Li, W. (2022) · Cellular and Molecular Biology · doi:10.14715/cmb/2021.67.5.53 · Cited by 6 · see citing works
“Furthermore, in another study carried out by He, H., et al., aging-related inflammation could promote senescence of hepatic stellate cells through the TNFα→ETS1→IL-27ra pathway (14).”
Hematopoietic Stem Cells as an Integrative Hub Linking Lifestyle to Cardiovascular Health
Chen, X., Liu, C., Wang, J., & Du, C. (2024) · Cells · doi:10.3390/cells13080712 · Cited by 6 · see citing works
“TNF-α activates a strong and specific NF-κ B-dependent gene program to directly promote the survival and myeloid differentiation of HSCs [33,34].”
BackgroundSelf-citationEmerging Evidence of the Significance of Thioredoxin-1 in Hematopoietic Stem Cell Aging
Jabbar, S., Mathews, P., & Kang, Y. (2022) · Antioxidants · doi:10.3390/antiox11071291 · Cited by 6 · see citing works
Zeng, X., Li, X., Shao, M., Xu, Y., Shan, W., Wei, C., Li, X., Wang, L., Hu, Y., Zhao, Y., et al. (2021) · Frontiers in Genetics · doi:10.3389/fgene.2021.745786 · Cited by 6 · see citing works
“Besides, although previous reports have demonstrated that a state of chronic inflammation is correlated with aging and is a strong risk factor for the occurrence of many chronic diseases (Franceschi et al., 2007; Franceschi and Campisi, 2014; Shavlakadze et al., 2019; He et al., 2020), the exact mechanisms underlying…”
BackgroundIL-27 regulates cytokine production as a double-edged sword in keratinocytes
Aioi, A., & Imamichi, T. (2022) · Trends in Immunotherapy · doi:10.24294/ti.v6.i1.1436 · Cited by 5 · see citing works
“However, because it has been reported in a previous study that TNF-α signaling via IL-27R promotes the aging of hematopoietic stem cells[32], and it remains unclear whether a sufficient amount of IL-27 is supplied by dendritic cells and macrophages, which are major sources of IL-27 whose functions decline with aging[3…”
BackgroundIL-27 promotes Treg cell expression of CD122 and fitness at homeostasis
Lanzar, Z. R., Aldridge, D. L., Cruz-Morales, E., Howard, C. A., Conway, I. O., Zhong, Z., Eberhard, J. N., Pereira, J. A., Phan, A. T., Ring, A. M., et al. (2025) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2519141122 · Cited by 4 · see citing works
Xia, Y., Chen, J., Dong, P., Zhang, L., Ding, Y., Ding, W., Han, X., Wang, X., & Li, D. (2024) · Molecular Neurobiology · doi:10.1007/s12035-024-04540-7 · Cited by 4 · see citing works
“Furthermore, previous studies have shown that the expression of ETS1 is regulated by the TNF-α/ERK1/2 signaling pathway [35].”
Self-citationSun, T., Li, D., Huang, L., & Zhu, X. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1141779 · Cited by 4 · see citing works
Li, X., Zhang, W., Wang, Y., Li, C., Wu, Y., Shang, Y., Lin, H., Li, Y., Wang, Y., Zeng, X., et al. (2024) · iScience · doi:10.1016/j.isci.2024.109126 · Cited by 4 · see citing works
Redox Regulation of Megakaryocyte Differentiation and Platelet Biogenesis
Chung, H., Shin, E., 박태호, Jeong, H., Jung, H., Bae, O.-N., & Noh, J. (2026) · Antioxidants · doi:10.3390/antiox15030352 · Cited by 3 · see citing works
Bonaroti, J. W., Ozel, M., Chen, T., Darby, J. L., Sun, X., Moheimani, H., Reitz, K. M., Kar, U. K., Zuckerbraun, B. S., Das, J., et al. (2023) · Journal of the American College of Surgeons · doi:10.1097/xcs.0000000000000922 · Cited by 3 · see citing works
“…TNF-α exposure impairs HSC function, contributes to myeloid-biased differentiation of HSCs, and induces pro-inflammatory gene expression in HSCs. 40,41 The enhanced pro-inflammatory patterns in HSCs and myeloid progenitors that we observed in older patients were associated with increased TNF-α…”
BackgroundThe role of genetic/epigenetic factors and microenvironment in hematopoietic stem cell ageing
Niazi, V., Parseh, B., & Ghafouri‐Fard, S. (2025) · Biogerontology · doi:10.1007/s10522-025-10218-x · Cited by 3 · see citing works
IL-27 limits HSPC differentiation during infection and protects from stem cell exhaustion
Aldridge, D. L., Lanzar, Z. R., Phan, A. T., Christian, D. A., Pardy, R. D., Min, B., Kedl, R. M., & Hunter, C. A. (2025) · eLife · doi:10.7554/elife.105876.3 · Cited by 2 · see citing works
What we thought we knew about TNF—And what we now must re-learn
Nilsson, A. R. (2026) · Stem Cell Reports · doi:10.1016/j.stemcr.2026.102827 · Cited by 2 · see citing works
Zhong, Y., Yang, S., Li, S., Yuan, S., Chen, X., Long, H., Wu, H., Guo, Y., & Wang, T. (2025) · Communications Biology · doi:10.1038/s42003-025-07918-y · Cited by 2 · see citing works
“IL-27R α is expressed in various cell types, including B cells, T cells, hematopoietic stem cells, and mesenchymal stem cells 12,13 .”
IL-27 limits HSPC differentiation during infection and protects from stem cell exhaustionPreprint
Aldridge, D. L., Lanzar, Z. R., Phan, A. T., Christian, D. A., Pardy, R. D., Min, B., Kedl, R. M., & Hunter, C. A. (2025) · eLife · doi:10.7554/elife.105876 · Cited by 2 · see citing works
“Indeed, reports that TNF α can upregulate HSPC expression of the IL-27R ( He et al., 2020 ) suggest that IL-27 responsiveness can be regulated by the local environment.”
Bueno, V. (2024) · Springer eBooks · doi:10.1007/978-3-031-55022-5_7 · Cited by 1 · see citing works
Mulia, G. E., Galindo, V., Chen, Y.-C., Salameh, J. W., & Figueiredo, M. L. (2025) · Stem Cell Research & Therapy · doi:10.1186/s13287-025-04647-1 · Cited by 1 · see citing works
“The receptor is expressed in a variety of cell types, including immune cells (T cells, B cells, NK cells, macrophages, dendritic cells), epithelial cells, endothelial cells, and stem cells [4, 5].”
Zhang, C., Ji, Y., Gao, X., Wan, Z., Gu, F., Lou, D., Liang, H., Liu, L., & Qin, W. (2025) · Cell & Bioscience · doi:10.1186/s13578-025-01499-3 · Cited by 1 · see citing works
“Peripheral blood was obtained from the tail of mice and counted using an Auto Hematology Analyzer BC-5000 (MINDRAY) [33].”
Trained immunity in the treatment for haematological malignancy
Liu, Z., Chen, X., Yang, C., Wang, H., Liu, H., & Fu, R. (2026) · Ageing Research Reviews · doi:10.1016/j.arr.2026.103210 · Cited by 1 · see citing works
Prospects for assessing the biological and immunological age of a person by blood factors
Kurgan, N. D., Panova, E. I., Silakova, L. V., Каганский, А. М., & Александрович, Р. С. (2021) · Science and Innovations in Medicine · doi:10.35693/2500-1388-2021-6-4-19-39 · Cited by 2 · see citing works
“Высокий уровень IL27 в крови связан с риском развития ишемической болезни сердца и воспалением сосудистого эндотелия [121].”
InfluentialStem cells, fitness, and aging
Kitaeva, K. V., Kiyasov, A. P., Rizvanov, A. A., Rutland, C. S., & Solovyeva, V. V. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-823761-8.00007-0 · Cited by 1 · see citing works
He, Y., & Zhou, D. (2020) · Blood Science · doi:10.1097/bs9.0000000000000060 · Cited by 1 · see citing works
IL-27 skews TNF-alpha-induced inflammatory microenvironment in keratinocytesPreprint
Aioi, A., & Imamichi, T. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.03.18.484839 · Cited by 1 · see citing works
“However, because it has been reported in a previous study that TNF-α signaling via IL-27R promotes the aging of hematopoietic stem cells [29], and it remains unclear whether sufficient amount of IL-27 is supplied by dendritic cells and macrophages, which are major sources of IL-27 whose functions decline with aging [3…”
BackgroundIL-27 limits HSPC differentiation during infection and protects from stem cell exhaustionPreprint
Aldridge, D. L., Lanzar, Z. R., Phan, A. T., Christian, D. A., Pardy, R. D., Min, B., Kedl, R. M., & Hunter, C. A. (2025) · eLife · doi:10.7554/elife.105876.2 · Cited by 1 · see citing works
The search for monomer-interaction-based alternative TNF-α therapies
Farrugia, M., & Baron, B. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-824390-9.00013-x
Definitive Treatments for Chronic Granulomatous Disease with a Focus on Gene Therapy
Santilli, G., & Thrasher, A. J. (2023) · Springer eBooks · doi:10.1007/978-3-031-23752-2_33
Gong, X., Wei, S., Dou, L., & Mou, F. (2023) · Research Square · doi:10.21203/rs.3.rs-3233579/v1
Time-series analysis of hematopoietic stem cells
Han, J., Duan, S., Li, Y., & Xin, C. (2024) · Medicine · doi:10.1097/md.0000000000036509
“[19] However, the mechanisms underlying HSC aging have not been fully elucidated.”
Sun, Q., Zhou, H., Wang, A., Li, W., & Xie, Y. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.04.09.588705
IL-27 limits HSPC differentiation during infection and protects from stem cell exhaustionPreprint
Aldridge, D. L., Lanzar, Z. R., Phan, A. T., Christian, D. A., Pardy, R. D., Min, B., Kedl, R. M., & Hunter, C. A. (2025) · eLife · doi:10.7554/elife.105876.1
Stem cell-based strategies for vascular aging: from mechanistic insights to clinical translation
Feng, X., Wei, Z., Hu, Y., Chen, T., & Yu, B. (2025) · Vessel Plus · doi:10.20517/2574-1209.2025.100
IL27RA is a promising key target for statins in treating hyperlipidemia
Zhao, N., Li, Y. M., & Liu, Y. (2026) · 3 Biotech · doi:10.1007/s13205-025-04668-w
“Targeting this pathway emerges as a promising strategy to mitigate aging-related hematopoietic decline (He et al. 2020).”
The Aging Blood: Cellular Origins, Circulating Drivers, and Therapeutic Potential
He, H., & Wang, J. (2026) · Aging and Cancer · doi:10.1002/aac2.70016
“Their frequency increases with age, whereas IL27Ra − HSCs maintain superior regenerative capacity and balanced differentiation potential across age groups [ 22 ].”
InfluentialSelf-citationAging Is a Key Driver for Adult Acute Myeloid Leukemia
Yin, R. L., & Zhang, H. (2026) · Aging and Cancer · doi:10.1002/aac2.70020
- Authors
- He, H., Xu, P., Zhang, X., Liao, M., Dong, Q., Cong, T., Tang, B., Yang, X., Ye, M., Chang, Y., Liu, W., Wang, X., Ju, Z., & Wang, J.
- Affiliations
- School of Pharmaceutical Sciences,
- Center for Life Sciences (CN)
- Beijing National Research Center for Information Science and Technology (CN)
- Fudan University (CN)
- Peking University People’s Hospital & Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China;
- Central Hospital of Zibo (CN)
- Jinan University (CN)
- Tsinghua University (CN)
- ORCID
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2020-07-09
- Volume
- 136
- Issue
- 2
- Pages
- 183-198
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W3016850173
- Cited by
- 94
- References
- 55
- Citations by year
- 2026: 6 · 2025: 22 · 2024: 15 · 2023: 12 · 2022: 20 · 2021: 11 · 2020: 7 · 2018: 1
- FWCI
- 7.89
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (61773230, 61721003, 91849106)
- Beijing Advanced Innovation Center for Structural Biology, Tsinghua University
- 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 cell aging, TNF-α, myeloid bias, myeloproliferative neoplasms, immunosenescence, hematopoietic recovery, aged mice
- MeSH terms
- Aging, Animals, Inflammation, Tumor Necrosis Factor-alpha, Receptors, Interleukin, Mice, Knockout, MAP Kinase Signaling System, Myeloid Progenitor Cells, Mice
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