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@ARTICLE{Komic:299583,
      author       = {H. Komic and T. Schmachtel and C. Simoes and M. Külp$^*$
                      and W. Yu and A. S. Jolly$^*$ and M. S. Nilsson and C.
                      Gonzalez and F. Prosper and H. Bonig and B. Paiva and F. B.
                      Thorén and M. A. Rieger$^*$},
      title        = {{C}ontinuous map of early hematopoietic stem cell
                      differentiation across human lifetime.},
      journal      = {Nature Communications},
      volume       = {16},
      number       = {1},
      issn         = {2041-1723},
      address      = {[London]},
      publisher    = {Springer Nature},
      reportid     = {DKFZ-2025-00524},
      pages        = {2287},
      year         = {2025},
      abstract     = {Uncovering early gene network changes of human
                      hematopoietic stem cells (HSCs) leading to differentiation
                      induction is of utmost importance for therapeutic
                      manipulation. We employed single cell proteo-transcriptomic
                      sequencing to FACS-enriched bone marrow hematopoietic stem
                      and progenitor cells (HSPCs) from 15 healthy donors.
                      Pseudotime analysis reveals four major differentiation
                      trajectories, which remain consistent upon aging, with an
                      early branching point into megakaryocyte-erythroid
                      progenitors. However, young donors suggest a more productive
                      differentiation from HSPCs to committed progenitors of all
                      lineages. tradeSeq analysis depicts continuous changes in
                      gene expression of HSPC-related genes (DLK1, ADGRG6), and
                      provides a roadmap of gene expression at the earliest
                      branching points. We identify CD273/PD-L2 to be highly
                      expressed in a subfraction of immature multipotent HSPCs
                      with enhanced quiescence. Functional experiments confirm the
                      immune-modulatory function of CD273/PD-L2 on HSPCs in
                      regulating T-cell activation and cytokine release. Here, we
                      present a molecular map of early HSPC differentiation across
                      human life.},
      keywords     = {Humans / Hematopoietic Stem Cells: cytology / Hematopoietic
                      Stem Cells: metabolism / Cell Differentiation / Adult /
                      Middle Aged / Single-Cell Analysis: methods / Male / Female
                      / Young Adult / Aged / Aging: physiology / Aging: genetics /
                      T-Lymphocytes: cytology / T-Lymphocytes: metabolism / Cell
                      Lineage: genetics / Lymphocyte Activation / Gene Expression
                      Profiling},
      cin          = {FM01},
      ddc          = {500},
      cid          = {I:(DE-He78)FM01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40055319},
      doi          = {10.1038/s41467-025-57096-y},
      url          = {https://inrepo02.dkfz.de/record/299583},
}