October 26, 2020 Preprint Open Access

García-Prat, Laura; Perdiguero, Eusebio; Alonso-Martín, Sonia; Dell'Orso, Stefania; Ravichandran, Srikanth; Brooks, Stephen R.; Juan, Aster H.; Campanario, Silvia; Jiang, Kan; Hong, Xiaotong; Ortet, Laura; Ruiz-Bonilla, Vanessa; Flández, Marta; Moiseeva, Victoria; Rebollo, Elena; Jardí, Mercè; Sun, Hong-Wei; Musarò, Antonio; Sandri, Marco; del Sol, Antonio; Sartorelli, Vittorio; Muñoz-Cánoves, Pura

JSON Export

{
  "files": [
    {
      "links": {
        "self": "https://zenodo.org/api/files/93f5b46d-3dd1-47b9-adff-14d37c8aa480/Garcia-Prat%202021%20Preprint.pdf"
      }, 
      "checksum": "md5:66cdcd546e49e598900cce1e944396df", 
      "bucket": "93f5b46d-3dd1-47b9-adff-14d37c8aa480", 
      "key": "Garcia-Prat 2021 Preprint.pdf", 
      "type": "pdf", 
      "size": 17420204
    }
  ], 
  "owners": [
    162696
  ], 
  "doi": "10.1038/s41556-020-00593-7", 
  "stats": {
    "version_unique_downloads": 562.0, 
    "unique_views": 24.0, 
    "views": 29.0, 
    "version_views": 29.0, 
    "unique_downloads": 562.0, 
    "version_unique_views": 24.0, 
    "volume": 10121138524.0, 
    "version_downloads": 581.0, 
    "downloads": 581.0, 
    "version_volume": 10121138524.0
  }, 
  "links": {
    "doi": "https://doi.org/10.1038/s41556-020-00593-7", 
    "latest_html": "https://zenodo.org/record/5844632", 
    "bucket": "https://zenodo.org/api/files/93f5b46d-3dd1-47b9-adff-14d37c8aa480", 
    "badge": "https://zenodo.org/badge/doi/10.1038/s41556-020-00593-7.svg", 
    "html": "https://zenodo.org/record/5844632", 
    "latest": "https://zenodo.org/api/records/5844632"
  }, 
  "created": "2022-01-13T10:35:08.401971+00:00", 
  "updated": "2022-01-13T13:48:59.525096+00:00", 
  "conceptrecid": "5844631", 
  "revision": 2, 
  "id": 5844632, 
  "metadata": {
    "access_right_category": "success", 
    "doi": "10.1038/s41556-020-00593-7", 
    "description": "<p><strong>Abstract</strong></p>\n\n<p>Tissue regeneration declines with ageing but little is known about whether this arises from changes in stem-cell heterogeneity. Here, in homeostatic skeletal muscle, we identify two quiescent stem-cell states distinguished by relative CD34 expression: CD34High, with stemness properties (genuine state), and CD34Low, committed to myogenic differentiation (primed state). The genuine-quiescent state is unexpectedly preserved into later life, succumbing only in extreme old age due to the acquisition of primed-state traits. Niche-derived IGF1-dependent Akt activation debilitates the genuine stem-cell state by imposing primed-state features via FoxO inhibition. Interventions to neutralize Akt and promote FoxO activity drive a primed-to-genuine state conversion, whereas FoxO inactivation deteriorates the genuine state at a young age, causing regenerative failure of muscle, as occurs in geriatric mice. These findings reveal transcriptional determinants of stem-cell heterogeneity that resist ageing more than previously anticipated and are only lost in extreme old age, with implications for the repair of geriatric muscle.</p>", 
    "license": {
      "id": "CC-BY-4.0"
    }, 
    "title": "FoxO maintains a genuine muscle stem-cell quiescent state until geriatric age", 
    "journal": {
      "volume": "22", 
      "pages": "1307-1318", 
      "title": "Nature Cell Biology"
    }, 
    "relations": {
      "version": [
        {
          "count": 1, 
          "index": 0, 
          "parent": {
            "pid_type": "recid", 
            "pid_value": "5844631"
          }, 
          "is_last": true, 
          "last_child": {
            "pid_type": "recid", 
            "pid_value": "5844632"
          }
        }
      ]
    }, 
    "grants": [
      {
        "code": "645648", 
        "links": {
          "self": "https://zenodo.org/api/grants/10.13039/501100000780::645648"
        }, 
        "title": "Muscle Stress Relief: An integrated research program linking together basic research on secondary myopathies in stress states to innovative translation in applied myology.", 
        "acronym": "Muscle stress relief", 
        "program": "H2020", 
        "funder": {
          "doi": "10.13039/501100000780", 
          "acronyms": [], 
          "name": "European Commission", 
          "links": {
            "self": "https://zenodo.org/api/funders/10.13039/501100000780"
          }
        }
      }, 
      {
        "code": "825825", 
        "links": {
          "self": "https://zenodo.org/api/grants/10.13039/501100000780::825825"
        }, 
        "title": "Unlocking Precision Gene Therapy", 
        "acronym": "UPGRADE", 
        "program": "H2020", 
        "funder": {
          "doi": "10.13039/501100000780", 
          "acronyms": [], 
          "name": "European Commission", 
          "links": {
            "self": "https://zenodo.org/api/funders/10.13039/501100000780"
          }
        }
      }, 
      {
        "code": "741966", 
        "links": {
          "self": "https://zenodo.org/api/grants/10.13039/501100000780::741966"
        }, 
        "title": "Tissue regeneration and aging: the decisive quiescent stem-cell state", 
        "acronym": "STEM-AGING", 
        "program": "H2020", 
        "funder": {
          "doi": "10.13039/501100000780", 
          "acronyms": [], 
          "name": "European Commission", 
          "links": {
            "self": "https://zenodo.org/api/funders/10.13039/501100000780"
          }
        }
      }
    ], 
    "communities": [
      {
        "id": "upgrade-h2020-project"
      }
    ], 
    "publication_date": "2020-10-26", 
    "creators": [
      {
        "affiliation": "Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada - Department of Experimental and Health Sciences, Pompeu Fabra University (UPF), CIBER on Neurodegenerative Diseases (CIBERNED), Barcelona, Spain - Spanish National Center on Cardiovascular Research (CNIC), Madrid, Spain", 
        "name": "Garc\u00eda-Prat,\u00a0Laura"
      }, 
      {
        "affiliation": "Department of Experimental and Health Sciences, Pompeu Fabra University (UPF), CIBER on Neurodegenerative Diseases (CIBERNED), Barcelona, Spain", 
        "name": "Perdiguero,\u00a0Eusebio"
      }, 
      {
        "affiliation": "Neurosciences Area, Biodonostia Health Research Institute, Donostia-San Sebasti\u00e1n, San Sebasti\u00e1n, Spain - Spanish National Center on Cardiovascular Research (CNIC), Madrid, Spain", 
        "name": "Alonso-Mart\u00edn,\u00a0Sonia"
      }, 
      {
        "affiliation": "Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH Bethesda, Bethesda, MD, USA", 
        "name": "Dell'Orso,\u00a0Stefania"
      }, 
      {
        "affiliation": "Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg", 
        "name": "Ravichandran,\u00a0Srikanth"
      }, 
      {
        "affiliation": "Biodata Mining and Discovery Section, NIAMS, NIH Bethesda, Bethesda, MD, USA", 
        "name": "Brooks,\u00a0Stephen R."
      }, 
      {
        "affiliation": "Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH Bethesda, Bethesda, MD, USA", 
        "name": "Juan,\u00a0Aster H."
      }, 
      {
        "affiliation": "Department of Experimental and Health Sciences, Pompeu Fabra University (UPF), CIBER on Neurodegenerative Diseases (CIBERNED), Barcelona, Spain - Spanish National Center on Cardiovascular Research (CNIC), Madrid, Spain", 
        "name": "Campanario,\u00a0Silvia"
      }, 
      {
        "affiliation": "Biodata Mining and Discovery Section, NIAMS, NIH Bethesda, Bethesda, MD, USA", 
        "name": "Jiang,\u00a0Kan"
      }, 
      {
        "affiliation": "Spanish National Center on Cardiovascular Research (CNIC), Madrid, Spain", 
        "name": "Hong,\u00a0Xiaotong"
      }, 
      {
        "affiliation": "Department of Experimental and Health Sciences, Pompeu Fabra University (UPF), CIBER on Neurodegenerative Diseases (CIBERNED), Barcelona, Spain", 
        "name": "Ortet,\u00a0Laura"
      }, 
      {
        "affiliation": "Department of Experimental and Health Sciences, Pompeu Fabra University (UPF), CIBER on Neurodegenerative Diseases (CIBERNED), Barcelona, Spain", 
        "name": "Ruiz-Bonilla,\u00a0Vanessa"
      }, 
      {
        "affiliation": "Grupo de Investigaci\u00f3n en Oncolog\u00eda Cl\u00ednico Traslacional, Instituto de Investigaci\u00f3n Hospital 12 de Octubre, Madrid, Spain - Spanish National Center on Cardiovascular Research (CNIC), Madrid, Spain", 
        "name": "Fl\u00e1ndez,\u00a0Marta"
      }, 
      {
        "affiliation": "Department of Experimental and Health Sciences, Pompeu Fabra University (UPF), CIBER on Neurodegenerative Diseases (CIBERNED), Barcelona, Spain", 
        "name": "Moiseeva,\u00a0Victoria"
      }, 
      {
        "affiliation": "Molecular Imaging Platform, Molecular Biology Institute of Barcelona (IBMB-CSIC), Barcelona, Spain", 
        "name": "Rebollo,\u00a0Elena"
      }, 
      {
        "affiliation": "Department of Experimental and Health Sciences, Pompeu Fabra University (UPF), CIBER on Neurodegenerative Diseases (CIBERNED), Barcelona, Spain", 
        "name": "Jard\u00ed,\u00a0Merc\u00e8"
      }, 
      {
        "affiliation": "Biodata Mining and Discovery Section, NIAMS, NIH Bethesda, Bethesda, MD, USA", 
        "name": "Sun,\u00a0Hong-Wei"
      }, 
      {
        "affiliation": "DAHFMO-Unit of Histology and Medical Embryology, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome, Italy", 
        "name": "Musar\u00f2,\u00a0Antonio"
      }, 
      {
        "affiliation": "Department of Biomedical Science, University of Padova, Padova, Italy", 
        "name": "Sandri,\u00a0Marco"
      }, 
      {
        "affiliation": "Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg - CIC bioGUNE, Derio, Spain - IKERBASQUE, Basque Foundation for Science, Bilbao, Spain", 
        "name": "del Sol,\u00a0Antonio"
      }, 
      {
        "affiliation": "Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH Bethesda, Bethesda, MD, USA", 
        "name": "Sartorelli,\u00a0Vittorio"
      }, 
      {
        "affiliation": "Department of Experimental and Health Sciences, Pompeu Fabra University (UPF), CIBER on Neurodegenerative Diseases (CIBERNED), Barcelona, Spain - Spanish National Center on Cardiovascular Research (CNIC), Madrid, Spain - ICREA, Barcelona, Spain", 
        "name": "Mu\u00f1oz-C\u00e1noves,\u00a0Pura"
      }
    ], 
    "access_right": "open", 
    "resource_type": {
      "subtype": "preprint", 
      "type": "publication", 
      "title": "Preprint"
    }
  }
}