Preprint Open Access

FoxO maintains a genuine muscle stem-cell quiescent state until geriatric age

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


MARC21 XML Export

<?xml version='1.0' encoding='UTF-8'?>
<record xmlns="http://www.loc.gov/MARC21/slim">
  <leader>00000nam##2200000uu#4500</leader>
  <controlfield tag="005">20220113134859.0</controlfield>
  <controlfield tag="001">5844632</controlfield>
  <datafield tag="700" ind1=" " ind2=" ">
    <subfield code="u">Department of Experimental and Health Sciences, Pompeu Fabra University (UPF), CIBER on Neurodegenerative Diseases (CIBERNED), Barcelona, Spain</subfield>
    <subfield code="a">Perdiguero, Eusebio</subfield>
  </datafield>
  <datafield tag="700" ind1=" " ind2=" ">
    <subfield code="u">Neurosciences Area, Biodonostia Health Research Institute, Donostia-San Sebastián, San Sebastián, Spain - Spanish National Center on Cardiovascular Research (CNIC), Madrid, Spain</subfield>
    <subfield code="a">Alonso-Martín, Sonia</subfield>
  </datafield>
  <datafield tag="700" ind1=" " ind2=" ">
    <subfield code="u">Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH Bethesda, Bethesda, MD, USA</subfield>
    <subfield code="a">Dell'Orso, Stefania</subfield>
  </datafield>
  <datafield tag="700" ind1=" " ind2=" ">
    <subfield code="u">Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg</subfield>
    <subfield code="a">Ravichandran, Srikanth</subfield>
  </datafield>
  <datafield tag="700" ind1=" " ind2=" ">
    <subfield code="u">Biodata Mining and Discovery Section, NIAMS, NIH Bethesda, Bethesda, MD, USA</subfield>
    <subfield code="a">Brooks, Stephen R.</subfield>
  </datafield>
  <datafield tag="700" ind1=" " ind2=" ">
    <subfield code="u">Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH Bethesda, Bethesda, MD, USA</subfield>
    <subfield code="a">Juan, Aster H.</subfield>
  </datafield>
  <datafield tag="700" ind1=" " ind2=" ">
    <subfield code="u">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</subfield>
    <subfield code="a">Campanario, Silvia</subfield>
  </datafield>
  <datafield tag="700" ind1=" " ind2=" ">
    <subfield code="u">Biodata Mining and Discovery Section, NIAMS, NIH Bethesda, Bethesda, MD, USA</subfield>
    <subfield code="a">Jiang, Kan</subfield>
  </datafield>
  <datafield tag="700" ind1=" " ind2=" ">
    <subfield code="u">Spanish National Center on Cardiovascular Research (CNIC), Madrid, Spain</subfield>
    <subfield code="a">Hong, Xiaotong</subfield>
  </datafield>
  <datafield tag="700" ind1=" " ind2=" ">
    <subfield code="u">Department of Experimental and Health Sciences, Pompeu Fabra University (UPF), CIBER on Neurodegenerative Diseases (CIBERNED), Barcelona, Spain</subfield>
    <subfield code="a">Ortet, Laura</subfield>
  </datafield>
  <datafield tag="700" ind1=" " ind2=" ">
    <subfield code="u">Department of Experimental and Health Sciences, Pompeu Fabra University (UPF), CIBER on Neurodegenerative Diseases (CIBERNED), Barcelona, Spain</subfield>
    <subfield code="a">Ruiz-Bonilla, Vanessa</subfield>
  </datafield>
  <datafield tag="700" ind1=" " ind2=" ">
    <subfield code="u">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</subfield>
    <subfield code="a">Flández, Marta</subfield>
  </datafield>
  <datafield tag="700" ind1=" " ind2=" ">
    <subfield code="u">Department of Experimental and Health Sciences, Pompeu Fabra University (UPF), CIBER on Neurodegenerative Diseases (CIBERNED), Barcelona, Spain</subfield>
    <subfield code="a">Moiseeva, Victoria</subfield>
  </datafield>
  <datafield tag="700" ind1=" " ind2=" ">
    <subfield code="u">Molecular Imaging Platform, Molecular Biology Institute of Barcelona (IBMB-CSIC), Barcelona, Spain</subfield>
    <subfield code="a">Rebollo, Elena</subfield>
  </datafield>
  <datafield tag="700" ind1=" " ind2=" ">
    <subfield code="u">Department of Experimental and Health Sciences, Pompeu Fabra University (UPF), CIBER on Neurodegenerative Diseases (CIBERNED), Barcelona, Spain</subfield>
    <subfield code="a">Jardí, Mercè</subfield>
  </datafield>
  <datafield tag="700" ind1=" " ind2=" ">
    <subfield code="u">Biodata Mining and Discovery Section, NIAMS, NIH Bethesda, Bethesda, MD, USA</subfield>
    <subfield code="a">Sun, Hong-Wei</subfield>
  </datafield>
  <datafield tag="700" ind1=" " ind2=" ">
    <subfield code="u">DAHFMO-Unit of Histology and Medical Embryology, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome, Italy</subfield>
    <subfield code="a">Musarò, Antonio</subfield>
  </datafield>
  <datafield tag="700" ind1=" " ind2=" ">
    <subfield code="u">Department of Biomedical Science, University of Padova, Padova, Italy</subfield>
    <subfield code="a">Sandri, Marco</subfield>
  </datafield>
  <datafield tag="700" ind1=" " ind2=" ">
    <subfield code="u">Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg - CIC bioGUNE, Derio, Spain - IKERBASQUE, Basque Foundation for Science, Bilbao, Spain</subfield>
    <subfield code="a">del Sol, Antonio</subfield>
  </datafield>
  <datafield tag="700" ind1=" " ind2=" ">
    <subfield code="u">Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH Bethesda, Bethesda, MD, USA</subfield>
    <subfield code="a">Sartorelli, Vittorio</subfield>
  </datafield>
  <datafield tag="700" ind1=" " ind2=" ">
    <subfield code="u">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</subfield>
    <subfield code="a">Muñoz-Cánoves, Pura</subfield>
  </datafield>
  <datafield tag="856" ind1="4" ind2=" ">
    <subfield code="s">17420204</subfield>
    <subfield code="z">md5:66cdcd546e49e598900cce1e944396df</subfield>
    <subfield code="u">https://zenodo.org/record/5844632/files/Garcia-Prat 2021 Preprint.pdf</subfield>
  </datafield>
  <datafield tag="542" ind1=" " ind2=" ">
    <subfield code="l">open</subfield>
  </datafield>
  <datafield tag="260" ind1=" " ind2=" ">
    <subfield code="c">2020-10-26</subfield>
  </datafield>
  <datafield tag="909" ind1="C" ind2="O">
    <subfield code="p">openaire</subfield>
    <subfield code="p">user-upgrade-h2020-project</subfield>
    <subfield code="o">oai:zenodo.org:5844632</subfield>
  </datafield>
  <datafield tag="909" ind1="C" ind2="4">
    <subfield code="c">1307-1318</subfield>
    <subfield code="v">22</subfield>
    <subfield code="p">Nature Cell Biology</subfield>
  </datafield>
  <datafield tag="100" ind1=" " ind2=" ">
    <subfield code="u">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</subfield>
    <subfield code="a">García-Prat, Laura</subfield>
  </datafield>
  <datafield tag="245" ind1=" " ind2=" ">
    <subfield code="a">FoxO maintains a genuine muscle stem-cell quiescent state until geriatric age</subfield>
  </datafield>
  <datafield tag="980" ind1=" " ind2=" ">
    <subfield code="a">user-upgrade-h2020-project</subfield>
  </datafield>
  <datafield tag="536" ind1=" " ind2=" ">
    <subfield code="c">645648</subfield>
    <subfield code="a">Muscle Stress Relief: An integrated research program linking together basic research on secondary myopathies in stress states to innovative translation in applied myology.</subfield>
  </datafield>
  <datafield tag="536" ind1=" " ind2=" ">
    <subfield code="c">825825</subfield>
    <subfield code="a">Unlocking Precision Gene Therapy</subfield>
  </datafield>
  <datafield tag="536" ind1=" " ind2=" ">
    <subfield code="c">741966</subfield>
    <subfield code="a">Tissue regeneration and aging: the decisive quiescent stem-cell state</subfield>
  </datafield>
  <datafield tag="540" ind1=" " ind2=" ">
    <subfield code="u">https://creativecommons.org/licenses/by/4.0/legalcode</subfield>
    <subfield code="a">Creative Commons Attribution 4.0 International</subfield>
  </datafield>
  <datafield tag="650" ind1="1" ind2="7">
    <subfield code="a">cc-by</subfield>
    <subfield code="2">opendefinition.org</subfield>
  </datafield>
  <datafield tag="520" ind1=" " ind2=" ">
    <subfield code="a">&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;</subfield>
  </datafield>
  <datafield tag="024" ind1=" " ind2=" ">
    <subfield code="a">10.1038/s41556-020-00593-7</subfield>
    <subfield code="2">doi</subfield>
  </datafield>
  <datafield tag="980" ind1=" " ind2=" ">
    <subfield code="a">publication</subfield>
    <subfield code="b">preprint</subfield>
  </datafield>
</record>
29
594
views
downloads
Views 29
Downloads 594
Data volume 10.3 GB
Unique views 24
Unique downloads 575

Share

Cite as