Home > Publications database > A Senescent Cluster in Aged Human Hematopoietic Stem Cell Compartment as Target for Senotherapy. > print

001     298226
005     20250202015018.0
024 7 _ |a 10.3390/ijms26020787
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024 7 _ |a 1422-0067
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024 7 _ |a 1661-6596
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037 _ _ |a DKFZ-2025-00233
041 _ _ |a English
082 _ _ |a 540
100 1 _ |a Poisa-Beiro, Laura
|b 0
245 _ _ |a A Senescent Cluster in Aged Human Hematopoietic Stem Cell Compartment as Target for Senotherapy.
260 _ _ |a Basel
|c 2025
|b Molecular Diversity Preservation International
336 7 _ |a article
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520 _ _ |a To 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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650 _ 7 |a aging
|2 Other
650 _ 7 |a comparative single-cell transcriptomics
|2 Other
650 _ 7 |a hematopoietic stem and progenitor cells (HSPC)
|2 Other
650 _ 7 |a senescence signature
|2 Other
650 _ 7 |a Senotherapeutics
|2 NLM Chemicals
650 _ 7 |a Tumor Suppressor Protein p53
|2 NLM Chemicals
650 _ 2 |a Hematopoietic Stem Cells: metabolism
|2 MeSH
650 _ 2 |a Hematopoietic Stem Cells: cytology
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Cellular Senescence
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Aging
|2 MeSH
650 _ 2 |a Senotherapeutics: pharmacology
|2 MeSH
650 _ 2 |a Hematopoiesis
|2 MeSH
650 _ 2 |a Transcriptome
|2 MeSH
650 _ 2 |a Aged
|2 MeSH
650 _ 2 |a Adult
|2 MeSH
650 _ 2 |a Tumor Suppressor Protein p53: metabolism
|2 MeSH
650 _ 2 |a Tumor Suppressor Protein p53: genetics
|2 MeSH
650 _ 2 |a DNA Damage
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Gene Expression Profiling
|2 MeSH
700 1 _ |a Landry, Jonathan J M
|0 0000-0003-2262-9099
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700 1 _ |a Yan, Bowen
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700 1 _ |a Kardorff, Michael
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700 1 _ |a Eckstein, Volker
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700 1 _ |a Villacorta, Laura
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700 1 _ |a Krammer, Peter
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700 1 _ |a Zaugg, Judith
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700 1 _ |a Gavin, Anne-Claude
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700 1 _ |a Benes, Vladimir
|0 0000-0002-0352-2547
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700 1 _ |a Zhou, Daohong
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700 1 _ |a Raffel, Simon
|b 11
700 1 _ |a Ho, Anthony D
|0 0000-0002-1656-0833
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773 _ _ |a 10.3390/ijms26020787
|g Vol. 26, no. 2, p. 787 -
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