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@ARTICLE{PoisaBeiro:298226,
      author       = {L. Poisa-Beiro and J. J. M. Landry and B. Yan and M.
                      Kardorff and V. Eckstein and L. Villacorta and P.
                      Krammer$^*$ and J. Zaugg and A.-C. Gavin and V. Benes and D.
                      Zhou and S. Raffel and A. D. Ho},
      title        = {{A} {S}enescent {C}luster in {A}ged {H}uman {H}ematopoietic
                      {S}tem {C}ell {C}ompartment as {T}arget for {S}enotherapy.},
      journal      = {International journal of molecular sciences},
      volume       = {26},
      number       = {2},
      issn         = {1422-0067},
      address      = {Basel},
      publisher    = {Molecular Diversity Preservation International},
      reportid     = {DKFZ-2025-00233},
      pages        = {787},
      year         = {2025},
      abstract     = {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.},
      keywords     = {Hematopoietic Stem Cells: metabolism / Hematopoietic Stem
                      Cells: cytology / Humans / Cellular Senescence / Animals /
                      Mice / Aging / Senotherapeutics: pharmacology /
                      Hematopoiesis / Transcriptome / Aged / Adult / Tumor
                      Suppressor Protein p53: metabolism / Tumor Suppressor
                      Protein p53: genetics / DNA Damage / Male / Gene Expression
                      Profiling / aging (Other) / comparative single-cell
                      transcriptomics (Other) / hematopoietic stem and progenitor
                      cells (HSPC) (Other) / senescence signature (Other) /
                      Senotherapeutics (NLM Chemicals) / Tumor Suppressor Protein
                      p53 (NLM Chemicals)},
      cin          = {D030},
      ddc          = {540},
      cid          = {I:(DE-He78)D030-20160331},
      pnm          = {314 - Immunologie und Krebs (POF4-314)},
      pid          = {G:(DE-HGF)POF4-314},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39859500},
      pmc          = {pmc:PMC11766015},
      doi          = {10.3390/ijms26020787},
      url          = {https://inrepo02.dkfz.de/record/298226},
}