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Essential Gene Profiles for Human Pluripotent Stem Cells Identify Uncharacterized Genes and Substrate Dependencies.
Mair, Barbara; Tomic, Jelena; Masud, Sanna N; Tonge, Peter; Weiss, Alexander; Usaj, Matej; Tong, Amy Hin Yan; Kwan, Jamie J; Brown, Kevin R; Titus, Emily; Atkins, Michael; Chan, Katherine S K; Munsie, Lise; Habsid, Andrea; Han, Hong; Kennedy, Marion; Cohen, Brenda; Keller, Gordon; Moffat, Jason.
Afiliação
  • Mair B; Donnelly Centre, University of Toronto, Toronto, ON, Canada.
  • Tomic J; Donnelly Centre, University of Toronto, Toronto, ON, Canada.
  • Masud SN; Donnelly Centre, University of Toronto, Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
  • Tonge P; Centre for Commercialization of Regenerative Medicine, Toronto, ON, Canada.
  • Weiss A; Donnelly Centre, University of Toronto, Toronto, ON, Canada.
  • Usaj M; Donnelly Centre, University of Toronto, Toronto, ON, Canada.
  • Tong AHY; Donnelly Centre, University of Toronto, Toronto, ON, Canada.
  • Kwan JJ; McEwen Stem Cell Institute, University Health Network, University of Toronto, Toronto, ON, Canada; Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada.
  • Brown KR; Donnelly Centre, University of Toronto, Toronto, ON, Canada.
  • Titus E; Centre for Commercialization of Regenerative Medicine, Toronto, ON, Canada.
  • Atkins M; McEwen Stem Cell Institute, University Health Network, University of Toronto, Toronto, ON, Canada; Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
  • Chan KSK; Donnelly Centre, University of Toronto, Toronto, ON, Canada.
  • Munsie L; Centre for Commercialization of Regenerative Medicine, Toronto, ON, Canada.
  • Habsid A; Donnelly Centre, University of Toronto, Toronto, ON, Canada.
  • Han H; Donnelly Centre, University of Toronto, Toronto, ON, Canada.
  • Kennedy M; McEwen Stem Cell Institute, University Health Network, University of Toronto, Toronto, ON, Canada; Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada.
  • Cohen B; McEwen Stem Cell Institute, University Health Network, University of Toronto, Toronto, ON, Canada; Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada.
  • Keller G; McEwen Stem Cell Institute, University Health Network, University of Toronto, Toronto, ON, Canada; Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
  • Moffat J; Donnelly Centre, University of Toronto, Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Canadian Institute for Advanced Research, Toronto, ON, Canada; Institute for Biomaterials and BioMedical Engineering, University of Toronto, ON, Canada. Electron
Cell Rep ; 27(2): 599-615.e12, 2019 04 09.
Article em En | MEDLINE | ID: mdl-30970261
Human pluripotent stem cells (hPSCs) provide an invaluable tool for modeling diseases and hold promise for regenerative medicine. For understanding pluripotency and lineage differentiation mechanisms, a critical first step involves systematically cataloging essential genes (EGs) that are indispensable for hPSC fitness, defined as cell reproduction in this study. To map essential genetic determinants of hPSC fitness, we performed genome-scale loss-of-function screens in an inducible Cas9 H1 hPSC line cultured on feeder cells and laminin to identify EGs. Among these, we found FOXH1 and VENTX, genes that encode transcription factors previously implicated in stem cell biology, as well as an uncharacterized gene, C22orf43/DRICH1. hPSC EGs are substantially different from other human model cell lines, and EGs in hPSCs are highly context dependent with respect to different growth substrates. Our CRISPR screens establish parameters for genome-wide screens in hPSCs, which will facilitate the characterization of unappreciated genetic regulators of hPSC biology.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Regulação da Expressão Gênica / Genes Essenciais / Células-Tronco Pluripotentes / Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article
Texto completo
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PubMed Links
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Regulação da Expressão Gênica / Genes Essenciais / Células-Tronco Pluripotentes / Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article