10.1038/s41556-020-00593-7
https://zenodo.org/records/5844632
oai:zenodo.org:5844632
García-Prat, Laura
Laura
García-Prat
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
Perdiguero, Eusebio
Eusebio
Perdiguero
Department of Experimental and Health Sciences, Pompeu Fabra University (UPF), CIBER on Neurodegenerative Diseases (CIBERNED), Barcelona, Spain
Alonso-Martín, Sonia
Sonia
Alonso-Martín
Neurosciences Area, Biodonostia Health Research Institute, Donostia-San Sebastián, San Sebastián, Spain - Spanish National Center on Cardiovascular Research (CNIC), Madrid, Spain
Dell'Orso, Stefania
Stefania
Dell'Orso
Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH Bethesda, Bethesda, MD, USA
Ravichandran, Srikanth
Srikanth
Ravichandran
Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
Brooks, Stephen R.
Stephen R.
Brooks
Biodata Mining and Discovery Section, NIAMS, NIH Bethesda, Bethesda, MD, USA
Juan, Aster H.
Aster H.
Juan
Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH Bethesda, Bethesda, MD, USA
Campanario, Silvia
Silvia
Campanario
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
Jiang, Kan
Kan
Jiang
Biodata Mining and Discovery Section, NIAMS, NIH Bethesda, Bethesda, MD, USA
Hong, Xiaotong
Xiaotong
Hong
Spanish National Center on Cardiovascular Research (CNIC), Madrid, Spain
Ortet, Laura
Laura
Ortet
Department of Experimental and Health Sciences, Pompeu Fabra University (UPF), CIBER on Neurodegenerative Diseases (CIBERNED), Barcelona, Spain
Ruiz-Bonilla, Vanessa
Vanessa
Ruiz-Bonilla
Department of Experimental and Health Sciences, Pompeu Fabra University (UPF), CIBER on Neurodegenerative Diseases (CIBERNED), Barcelona, Spain
Flández, Marta
Marta
Flández
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
Moiseeva, Victoria
Victoria
Moiseeva
Department of Experimental and Health Sciences, Pompeu Fabra University (UPF), CIBER on Neurodegenerative Diseases (CIBERNED), Barcelona, Spain
Rebollo, Elena
Elena
Rebollo
Molecular Imaging Platform, Molecular Biology Institute of Barcelona (IBMB-CSIC), Barcelona, Spain
Jardí, Mercè
Mercè
Jardí
Department of Experimental and Health Sciences, Pompeu Fabra University (UPF), CIBER on Neurodegenerative Diseases (CIBERNED), Barcelona, Spain
Sun, Hong-Wei
Hong-Wei
Sun
Biodata Mining and Discovery Section, NIAMS, NIH Bethesda, Bethesda, MD, USA
Musarò, Antonio
Antonio
Musarò
DAHFMO-Unit of Histology and Medical Embryology, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome, Italy
Sandri, Marco
Marco
Sandri
Department of Biomedical Science, University of Padova, Padova, Italy
del Sol, Antonio
Antonio
del Sol
Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg - CIC bioGUNE, Derio, Spain - IKERBASQUE, Basque Foundation for Science, Bilbao, Spain
Sartorelli, Vittorio
Vittorio
Sartorelli
Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH Bethesda, Bethesda, MD, USA
Muñoz-Cánoves, Pura
Pura
Muñoz-Cánoves
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
FoxO maintains a genuine muscle stem-cell quiescent state until geriatric age
Zenodo
2020
2020-10-26
https://zenodo.org/communities/upgrade-h2020-project
https://zenodo.org/communities/eu
Creative Commons Attribution 4.0 International
Abstract
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.
European Commission
10.13039/501100000780
645648
Muscle Stress Relief: An integrated research program linking together basic research on secondary myopathies in stress states to innovative translation in applied myology.
European Commission
10.13039/501100000780
825825
Unlocking Precision Gene Therapy
European Commission
10.13039/501100000780
741966
Tissue regeneration and aging: the decisive quiescent stem-cell state