{
  "abstract": "Hematopoietic stem cells (HSCs) are the definitive source of all blood cells and replenish them for life. The endothelial protein C receptor (EPCR) which signals via its coreceptor protease-activated receptor 1 (PAR1) is expressed on a subpopulation of highly quiescent HSCs with high engraftment potential after transplantation. We demonstrate that EPCR/PAR1 on human CD34+ hematopoietic stem and progenitor cells (HSPCs) can be activated by both thrombin (THR) and activated protein C (aPC), inducing distinct signaling. PAR1 activation by THR in HSPCs led to Ca2+ flux, phosphorylation of CREB and ERK1/2 and increased glycolysis. In contrast, aPC activated CREB and AKT, but not ERK1/2, Ca2+ flux or metabolic changes. Functionally, stimulation of human CD34+ cells with aPC decreased differentiation and enhanced clonogenic potential. aPC counteracted the enforced proliferation of HSPCs by interleukin 1α in vitro. Short stimulation of CD34+ cells with aPC enhanced their short-term serial engraftment in immunodeficient mice. Our findings identify aPC/PAR1 signaling as a key target supporting CD34+ HSPC maintenance, stress resistance and regeneration, while THR/PAR1 signaling has opposing effects.",
  "abstract_shown": true,
  "affiliations": [
    "Division of Gene and Cell Therapy, Institute for Regenerative Medicine (IREM), University of Zurich, 8952 Schlieren, Switzerland",
    "Institute for the Biology of Stem Cells, University of California, Santa Cruz, CA 95064 USA",
    "Biomolecular Engineering, University of California, Santa Cruz, CA 95064 USA",
    "Translational Stem Cell Biology, Institute for Regenerative Medicine (IREM), University of Zurich, 8952 Schlieren, Switzerland",
    "Department of Somatic Gene Therapy, University Children’s Hospital Zurich, 8008 Zurich, Switzerland",
    "Center for Applied Biotechnology and Molecular Medicine (CABMM), University of Zurich, 8057 Zurich, Switzerland"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Simon J Pöllmann"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Marcel G E Rommel"
    },
    {
      "affs": [
        0
      ],
      "name": "Leal Oburoglu"
    },
    {
      "affs": [
        0
      ],
      "name": "Tanja Hirch",
      "orcid": "0000-0002-7989-972X"
    },
    {
      "affs": [
        3
      ],
      "name": "Fabiola Valdivia-Francia"
    },
    {
      "affs": [
        0
      ],
      "name": "Kah Mun Siow"
    },
    {
      "affs": [
        0
      ],
      "name": "Timon Menzi",
      "orcid": "0009-0005-9634-0054"
    },
    {
      "affs": [
        0
      ],
      "name": "Julia Ackva",
      "orcid": "0009-0000-2223-923X"
    },
    {
      "affs": [
        0
      ],
      "name": "Franziska Schenk"
    },
    {
      "affs": [
        0
      ],
      "name": "Matthias J Neeracher",
      "orcid": "0009-0007-4274-5595"
    },
    {
      "affs": [
        3
      ],
      "name": "Ataman Sendoel"
    },
    {
      "affs": [
        0,
        4,
        5
      ],
      "name": "Janine Reichenbach",
      "orcid": "0000-0002-9008-1312"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "E Camilla Forsberg",
      "orcid": "0000-0002-8740-4299"
    },
    {
      "affs": [
        0
      ],
      "name": "Ute Modlich",
      "orcid": "0000-0001-8018-4118"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/01wy0n93dcb4b.bib",
  "cited_by": 0,
  "doi": "10.1038/s44321-026-00529-y",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13748566/",
  "id": "01wy0n93dcb4b",
  "issns": [
    "1757-4676",
    "1757-4684"
  ],
  "landing_url": "https://doi.org/10.1038/s44321-026-00529-y",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "2720|Hematopoietic Stem Cell Transplantation"
    ]
  ],
  "openalex": "W7221160369",
  "pdf_url": "https://link.springer.com/content/pdf/10.1038/s44321-026-00529-y.pdf",
  "pmcid": "PMC13748566",
  "pmid": "42855519",
  "published": "2026-10-09",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/01wy0n93dcb4b.ris",
  "sources": [
    {
      "first_seen": "2026-11-13T12:26:32Z",
      "native_id": "PMC13748566",
      "source": "pmc",
      "url": "https://doi.org/10.1038/s44321-026-00529-y"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2720|Hematopoietic Stem Cell Transplantation",
      "subfield": "general"
    }
  ],
  "title": "Activated protein C promotes hematopoietic stem and progenitor cell quiescence and engraftment",
  "title_text": "Activated protein C promotes hematopoietic stem and progenitor cell quiescence and engraftment",
  "type": "peer-reviewed",
  "updated_at": "2026-11-13T12:26:32Z",
  "url": "https://research.draconitic.com/paper/01wy0n93dcb4b",
  "venue": "EMBO Molecular Medicine",
  "versions": []
}