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

DataCite XML Export

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  <identifier identifierType="URL">https://zenodo.org/record/5844632</identifier>
  <creators>
    <creator>
      <creatorName>García-Prat, Laura</creatorName>
      <givenName>Laura</givenName>
      <familyName>García-Prat</familyName>
      <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</affiliation>
    </creator>
    <creator>
      <creatorName>Perdiguero, Eusebio</creatorName>
      <givenName>Eusebio</givenName>
      <familyName>Perdiguero</familyName>
      <affiliation>Department of Experimental and Health Sciences, Pompeu Fabra University (UPF), CIBER on Neurodegenerative Diseases (CIBERNED), Barcelona, Spain</affiliation>
    </creator>
    <creator>
      <creatorName>Alonso-Martín, Sonia</creatorName>
      <givenName>Sonia</givenName>
      <familyName>Alonso-Martín</familyName>
      <affiliation>Neurosciences Area, Biodonostia Health Research Institute, Donostia-San Sebastián, San Sebastián, Spain - Spanish National Center on Cardiovascular Research (CNIC), Madrid, Spain</affiliation>
    </creator>
    <creator>
      <creatorName>Dell'Orso, Stefania</creatorName>
      <givenName>Stefania</givenName>
      <familyName>Dell'Orso</familyName>
      <affiliation>Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH Bethesda, Bethesda, MD, USA</affiliation>
    </creator>
    <creator>
      <creatorName>Ravichandran, Srikanth</creatorName>
      <givenName>Srikanth</givenName>
      <familyName>Ravichandran</familyName>
      <affiliation>Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg</affiliation>
    </creator>
    <creator>
      <creatorName>Brooks, Stephen R.</creatorName>
      <givenName>Stephen R.</givenName>
      <familyName>Brooks</familyName>
      <affiliation>Biodata Mining and Discovery Section, NIAMS, NIH Bethesda, Bethesda, MD, USA</affiliation>
    </creator>
    <creator>
      <creatorName>Juan, Aster H.</creatorName>
      <givenName>Aster H.</givenName>
      <familyName>Juan</familyName>
      <affiliation>Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH Bethesda, Bethesda, MD, USA</affiliation>
    </creator>
    <creator>
      <creatorName>Campanario, Silvia</creatorName>
      <givenName>Silvia</givenName>
      <familyName>Campanario</familyName>
      <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</affiliation>
    </creator>
    <creator>
      <creatorName>Jiang, Kan</creatorName>
      <givenName>Kan</givenName>
      <familyName>Jiang</familyName>
      <affiliation>Biodata Mining and Discovery Section, NIAMS, NIH Bethesda, Bethesda, MD, USA</affiliation>
    </creator>
    <creator>
      <creatorName>Hong, Xiaotong</creatorName>
      <givenName>Xiaotong</givenName>
      <familyName>Hong</familyName>
      <affiliation>Spanish National Center on Cardiovascular Research (CNIC), Madrid, Spain</affiliation>
    </creator>
    <creator>
      <creatorName>Ortet, Laura</creatorName>
      <givenName>Laura</givenName>
      <familyName>Ortet</familyName>
      <affiliation>Department of Experimental and Health Sciences, Pompeu Fabra University (UPF), CIBER on Neurodegenerative Diseases (CIBERNED), Barcelona, Spain</affiliation>
    </creator>
    <creator>
      <creatorName>Ruiz-Bonilla, Vanessa</creatorName>
      <givenName>Vanessa</givenName>
      <familyName>Ruiz-Bonilla</familyName>
      <affiliation>Department of Experimental and Health Sciences, Pompeu Fabra University (UPF), CIBER on Neurodegenerative Diseases (CIBERNED), Barcelona, Spain</affiliation>
    </creator>
    <creator>
      <creatorName>Flández, Marta</creatorName>
      <givenName>Marta</givenName>
      <familyName>Flández</familyName>
      <affiliation>Grupo de Investigación en Oncología Clínico Traslacional, Instituto de Investigación Hospital 12 de Octubre, Madrid, Spain - Spanish National Center on Cardiovascular Research (CNIC), Madrid, Spain</affiliation>
    </creator>
    <creator>
      <creatorName>Moiseeva, Victoria</creatorName>
      <givenName>Victoria</givenName>
      <familyName>Moiseeva</familyName>
      <affiliation>Department of Experimental and Health Sciences, Pompeu Fabra University (UPF), CIBER on Neurodegenerative Diseases (CIBERNED), Barcelona, Spain</affiliation>
    </creator>
    <creator>
      <creatorName>Rebollo, Elena</creatorName>
      <givenName>Elena</givenName>
      <familyName>Rebollo</familyName>
      <affiliation>Molecular Imaging Platform, Molecular Biology Institute of Barcelona (IBMB-CSIC), Barcelona, Spain</affiliation>
    </creator>
    <creator>
      <creatorName>Jardí, Mercè</creatorName>
      <givenName>Mercè</givenName>
      <familyName>Jardí</familyName>
      <affiliation>Department of Experimental and Health Sciences, Pompeu Fabra University (UPF), CIBER on Neurodegenerative Diseases (CIBERNED), Barcelona, Spain</affiliation>
    </creator>
    <creator>
      <creatorName>Sun, Hong-Wei</creatorName>
      <givenName>Hong-Wei</givenName>
      <familyName>Sun</familyName>
      <affiliation>Biodata Mining and Discovery Section, NIAMS, NIH Bethesda, Bethesda, MD, USA</affiliation>
    </creator>
    <creator>
      <creatorName>Musarò, Antonio</creatorName>
      <givenName>Antonio</givenName>
      <familyName>Musarò</familyName>
      <affiliation>DAHFMO-Unit of Histology and Medical Embryology, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome, Italy</affiliation>
    </creator>
    <creator>
      <creatorName>Sandri, Marco</creatorName>
      <givenName>Marco</givenName>
      <familyName>Sandri</familyName>
      <affiliation>Department of Biomedical Science, University of Padova, Padova, Italy</affiliation>
    </creator>
    <creator>
      <creatorName>del Sol, Antonio</creatorName>
      <givenName>Antonio</givenName>
      <familyName>del Sol</familyName>
      <affiliation>Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg - CIC bioGUNE, Derio, Spain - IKERBASQUE, Basque Foundation for Science, Bilbao, Spain</affiliation>
    </creator>
    <creator>
      <creatorName>Sartorelli, Vittorio</creatorName>
      <givenName>Vittorio</givenName>
      <familyName>Sartorelli</familyName>
      <affiliation>Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH Bethesda, Bethesda, MD, USA</affiliation>
    </creator>
    <creator>
      <creatorName>Muñoz-Cánoves, Pura</creatorName>
      <givenName>Pura</givenName>
      <familyName>Muñoz-Cánoves</familyName>
      <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</affiliation>
    </creator>
  </creators>
  <titles>
    <title>FoxO maintains a genuine muscle stem-cell quiescent state until geriatric age</title>
  </titles>
  <publisher>Zenodo</publisher>
  <publicationYear>2020</publicationYear>
  <dates>
    <date dateType="Issued">2020-10-26</date>
  </dates>
  <resourceType resourceTypeGeneral="Preprint"/>
  <alternateIdentifiers>
    <alternateIdentifier alternateIdentifierType="url">https://zenodo.org/record/5844632</alternateIdentifier>
  </alternateIdentifiers>
  <relatedIdentifiers>
    <relatedIdentifier relatedIdentifierType="DOI" relationType="IsIdenticalTo">10.1038/s41556-020-00593-7</relatedIdentifier>
    <relatedIdentifier relatedIdentifierType="URL" relationType="IsPartOf">https://zenodo.org/communities/upgrade-h2020-project</relatedIdentifier>
  </relatedIdentifiers>
  <rightsList>
    <rights rightsURI="https://creativecommons.org/licenses/by/4.0/legalcode">Creative Commons Attribution 4.0 International</rights>
    <rights rightsURI="info:eu-repo/semantics/openAccess">Open Access</rights>
  </rightsList>
  <descriptions>
    <description descriptionType="Abstract">&lt;p&gt;&lt;strong&gt;Abstract&lt;/strong&gt;&lt;/p&gt;

&lt;p&gt;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.&lt;/p&gt;</description>
  </descriptions>
  <fundingReferences>
    <fundingReference>
      <funderName>European Commission</funderName>
      <funderIdentifier funderIdentifierType="Crossref Funder ID">10.13039/100010661</funderIdentifier>
      <awardNumber awardURI="info:eu-repo/grantAgreement/EC/H2020/645648/">645648</awardNumber>
      <awardTitle>Muscle Stress Relief: An integrated research program linking together basic research on secondary myopathies in stress states to innovative translation in applied myology.</awardTitle>
    </fundingReference>
    <fundingReference>
      <funderName>European Commission</funderName>
      <funderIdentifier funderIdentifierType="Crossref Funder ID">10.13039/100010661</funderIdentifier>
      <awardNumber awardURI="info:eu-repo/grantAgreement/EC/H2020/825825/">825825</awardNumber>
      <awardTitle>Unlocking Precision Gene Therapy</awardTitle>
    </fundingReference>
    <fundingReference>
      <funderName>European Commission</funderName>
      <funderIdentifier funderIdentifierType="Crossref Funder ID">10.13039/100010661</funderIdentifier>
      <awardNumber awardURI="info:eu-repo/grantAgreement/EC/H2020/741966/">741966</awardNumber>
      <awardTitle>Tissue regeneration and aging: the decisive quiescent stem-cell state</awardTitle>
    </fundingReference>
  </fundingReferences>
</resource>