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Early stem cell aging in the mature brain.
Ibrayeva, Albina; Bay, Maxwell; Pu, Elbert; Jörg, David J; Peng, Lei; Jun, Heechul; Zhang, Naibo; Aaron, Daniel; Lin, Congrui; Resler, Galen; Hidalgo, Axel; Jang, Mi-Hyeon; Simons, Benjamin D; Bonaguidi, Michael A.
Afiliação
  • Ibrayeva A; Eli and Edythe Broad Center for Regenerative Medicine & Stem Cell Research at USC, University of Southern California, Los Angeles, CA 90033, USA; Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA 90033, USA; USC Davis School - Buck Inst
  • Bay M; Eli and Edythe Broad Center for Regenerative Medicine & Stem Cell Research at USC, University of Southern California, Los Angeles, CA 90033, USA; Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA 90033, USA; Neuroscience Graduate Progra
  • Pu E; Eli and Edythe Broad Center for Regenerative Medicine & Stem Cell Research at USC, University of Southern California, Los Angeles, CA 90033, USA; Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA 90033, USA.
  • Jörg DJ; Cavendish Laboratory, Department of Physics, University of Cambridge, Cambridge CB3 0HE, UK; Gurdon Institute, University of Cambridge, Cambridge CB3 0HE, UK.
  • Peng L; Eli and Edythe Broad Center for Regenerative Medicine & Stem Cell Research at USC, University of Southern California, Los Angeles, CA 90033, USA; Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA 90033, USA; Neuroscience Graduate Progra
  • Jun H; Department of Neurological Surgery, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
  • Zhang N; Eli and Edythe Broad Center for Regenerative Medicine & Stem Cell Research at USC, University of Southern California, Los Angeles, CA 90033, USA; Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA 90033, USA.
  • Aaron D; Eli and Edythe Broad Center for Regenerative Medicine & Stem Cell Research at USC, University of Southern California, Los Angeles, CA 90033, USA; Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA 90033, USA.
  • Lin C; Eli and Edythe Broad Center for Regenerative Medicine & Stem Cell Research at USC, University of Southern California, Los Angeles, CA 90033, USA; Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA 90033, USA.
  • Resler G; Eli and Edythe Broad Center for Regenerative Medicine & Stem Cell Research at USC, University of Southern California, Los Angeles, CA 90033, USA; Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA 90033, USA.
  • Hidalgo A; Eli and Edythe Broad Center for Regenerative Medicine & Stem Cell Research at USC, University of Southern California, Los Angeles, CA 90033, USA; Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA 90033, USA.
  • Jang MH; Department of Neurological Surgery, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
  • Simons BD; Cavendish Laboratory, Department of Physics, University of Cambridge, Cambridge CB3 0HE, UK; Gurdon Institute, University of Cambridge, Cambridge CB3 0HE, UK.
  • Bonaguidi MA; Eli and Edythe Broad Center for Regenerative Medicine & Stem Cell Research at USC, University of Southern California, Los Angeles, CA 90033, USA; Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA 90033, USA; USC Davis School - Buck Inst
Cell Stem Cell ; 28(5): 955-966.e7, 2021 05 06.
Article em En | MEDLINE | ID: mdl-33848469
Stem cell dysfunction drives many age-related disorders. Identifying mechanisms that initially compromise stem cell behavior represent early targets to promote tissue function later in life. Here, we pinpoint multiple factors that disrupt neural stem cell (NSC) behavior in the adult hippocampus. Clonal tracing showed that NSCs exhibit asynchronous depletion by identifying short-term NSCs (ST-NSCs) and long-term NSCs (LT-NSCs). ST-NSCs divide rapidly to generate neurons and deplete in the young brain. Meanwhile, multipotent LT-NSCs are maintained for months but are pushed out of homeostasis by lengthening quiescence. Single-cell transcriptome analysis of deep NSC quiescence revealed several hallmarks of molecular aging in the mature brain and identified tyrosine-protein kinase Abl1 as an NSC aging factor. Treatment with the Abl inhibitor imatinib increased NSC activation without impairing NSC maintenance in the middle-aged brain. Our study indicates that hippocampal NSCs are particularly vulnerable and adaptable to cellular aging.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neurogênese / Células-Tronco Neurais Tipo de estudo: Prognostic_studies Idioma: En Revista: Cell Stem Cell Ano de publicação: 2021 Tipo de documento: Article
Texto completo
Imprimir
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PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neurogênese / Células-Tronco Neurais Tipo de estudo: Prognostic_studies Idioma: En Revista: Cell Stem Cell Ano de publicação: 2021 Tipo de documento: Article