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000298226 041__ $$aEnglish
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000298226 1001_ $$aPoisa-Beiro, Laura$$b0
000298226 245__ $$aA Senescent Cluster in Aged Human Hematopoietic Stem Cell Compartment as Target for Senotherapy.
000298226 260__ $$aBasel$$bMolecular Diversity Preservation International$$c2025
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000298226 520__ $$aTo identify the differences between aged and young human hematopoiesis, we performed a direct comparison of aged and young human hematopoietic stem and progenitor cells (HSPCs). Alterations in transcriptome profiles upon aging between humans and mice were then compared. Human specimens consist of CD34+ cells from bone marrow, and mouse specimens of hematopoietic stem cells (HSCs; Lin- Kit+ Sca1+ CD150+). Single-cell transcriptomic studies, functional clustering, and developmental trajectory analyses were performed. A significant increase in multipotent progenitor 2A (MPP2A) cluster is found in the early HSC trajectory in old human subjects. This cluster is enriched in senescence signatures (increased telomere attrition, DNA damage, activation of P53 pathway). In mouse models, the accumulation of an analogous subset was confirmed in the aged LT-HSC population. Elimination of this subset has been shown to rejuvenate hematopoiesis in mice. A significant activation of the P53-P21WAF1/CIP1 pathway was found in the MPP2A population in humans. In contrast, the senescent HSCs in mice are characterized by activation of the p16Ink4a pathway. Aging in the human HSC compartment is mainly caused by the clonal evolution and accumulation of a senescent cell cluster. A population with a similar senescence signature in the aged LT-HSCs was confirmed in the murine aging model. Clearance of this senescent population with senotherapy in humans is feasible and potentially beneficial.
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000298226 650_7 $$2Other$$aaging
000298226 650_7 $$2Other$$acomparative single-cell transcriptomics
000298226 650_7 $$2Other$$ahematopoietic stem and progenitor cells (HSPC)
000298226 650_7 $$2Other$$asenescence signature
000298226 650_7 $$2NLM Chemicals$$aSenotherapeutics
000298226 650_7 $$2NLM Chemicals$$aTumor Suppressor Protein p53
000298226 650_2 $$2MeSH$$aHematopoietic Stem Cells: metabolism
000298226 650_2 $$2MeSH$$aHematopoietic Stem Cells: cytology
000298226 650_2 $$2MeSH$$aHumans
000298226 650_2 $$2MeSH$$aCellular Senescence
000298226 650_2 $$2MeSH$$aAnimals
000298226 650_2 $$2MeSH$$aMice
000298226 650_2 $$2MeSH$$aAging
000298226 650_2 $$2MeSH$$aSenotherapeutics: pharmacology
000298226 650_2 $$2MeSH$$aHematopoiesis
000298226 650_2 $$2MeSH$$aTranscriptome
000298226 650_2 $$2MeSH$$aAged
000298226 650_2 $$2MeSH$$aAdult
000298226 650_2 $$2MeSH$$aTumor Suppressor Protein p53: metabolism
000298226 650_2 $$2MeSH$$aTumor Suppressor Protein p53: genetics
000298226 650_2 $$2MeSH$$aDNA Damage
000298226 650_2 $$2MeSH$$aMale
000298226 650_2 $$2MeSH$$aGene Expression Profiling
000298226 7001_ $$00000-0003-2262-9099$$aLandry, Jonathan J M$$b1
000298226 7001_ $$00000-0003-4730-6763$$aYan, Bowen$$b2
000298226 7001_ $$00009-0008-9720-6166$$aKardorff, Michael$$b3
000298226 7001_ $$aEckstein, Volker$$b4
000298226 7001_ $$aVillacorta, Laura$$b5
000298226 7001_ $$0P:(DE-He78)92492c6eae05ee58973fc142c9201e3d$$aKrammer, Peter$$b6
000298226 7001_ $$aZaugg, Judith$$b7
000298226 7001_ $$00000-0003-4917-2340$$aGavin, Anne-Claude$$b8
000298226 7001_ $$00000-0002-0352-2547$$aBenes, Vladimir$$b9
000298226 7001_ $$aZhou, Daohong$$b10
000298226 7001_ $$aRaffel, Simon$$b11
000298226 7001_ $$00000-0002-1656-0833$$aHo, Anthony D$$b12
000298226 773__ $$0PERI:(DE-600)2019364-6$$a10.3390/ijms26020787$$gVol. 26, no. 2, p. 787 -$$n2$$p787$$tInternational journal of molecular sciences$$v26$$x1422-0067$$y2025
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