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Naive Pluripotent Stem Cells Exhibit Phenotypic Variability that Is Driven by Genetic Variation.
Ortmann, Daniel; Brown, Stephanie; Czechanski, Anne; Aydin, Selcan; Muraro, Daniele; Huang, Yuanhua; Tomaz, Rute A; Osnato, Anna; Canu, Giovanni; Wesley, Brandon T; Skelly, Daniel A; Stegle, Oliver; Choi, Ted; Churchill, Gary A; Baker, Christopher L; Rugg-Gunn, Peter J; Munger, Steven C; Reinholdt, Laura G; Vallier, Ludovic.
Afiliação
  • Ortmann D; Wellcome Trust and MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK; Department of Surgery, University of Cambridge, Cambridge, UK. Electronic address: daniel.ortmann@gmail.com.
  • Brown S; Wellcome Trust and MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK; Department of Surgery, University of Cambridge, Cambridge, UK.
  • Czechanski A; Jackson Laboratory, Bar Harbor, ME, USA.
  • Aydin S; Jackson Laboratory, Bar Harbor, ME, USA.
  • Muraro D; Wellcome Trust and MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK; Department of Surgery, University of Cambridge, Cambridge, UK; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
  • Huang Y; Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, UK.
  • Tomaz RA; Wellcome Trust and MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK; Department of Surgery, University of Cambridge, Cambridge, UK.
  • Osnato A; Wellcome Trust and MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK; Department of Surgery, University of Cambridge, Cambridge, UK.
  • Canu G; Wellcome Trust and MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK; Department of Surgery, University of Cambridge, Cambridge, UK.
  • Wesley BT; Wellcome Trust and MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK; Department of Surgery, University of Cambridge, Cambridge, UK.
  • Skelly DA; Jackson Laboratory, Bar Harbor, ME, USA.
  • Stegle O; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, UK; European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany; Division of Computational Genomics and Systems Genetics, German Cancer Research, Center (DKFZ), Heidelberg,
  • Choi T; Jackson Laboratory, Bar Harbor, ME, USA.
  • Churchill GA; Jackson Laboratory, Bar Harbor, ME, USA.
  • Baker CL; Jackson Laboratory, Bar Harbor, ME, USA.
  • Rugg-Gunn PJ; Wellcome Trust and MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK; Epigenetics Programme, Babraham Institute, Cambridge, UK.
  • Munger SC; Jackson Laboratory, Bar Harbor, ME, USA.
  • Reinholdt LG; Jackson Laboratory, Bar Harbor, ME, USA.
  • Vallier L; Wellcome Trust and MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK; Department of Surgery, University of Cambridge, Cambridge, UK. Electronic address: lv225@cam.ac.uk.
Cell Stem Cell ; 27(3): 470-481.e6, 2020 09 03.
Article em En | MEDLINE | ID: mdl-32795399
Variability among pluripotent stem cell (PSC) lines is a prevailing issue that hampers not only experimental reproducibility but also large-scale applications and personalized cell-based therapy. This variability could result from epigenetic and genetic factors that influence stem cell behavior. Naive culture conditions minimize epigenetic fluctuation, potentially overcoming differences in PSC line differentiation potential. Here we derived PSCs from distinct mouse strains under naive conditions and show that lines from distinct genetic backgrounds have divergent differentiation capacity, confirming a major role for genetics in PSC phenotypic variability. This is explained in part through inconsistent activity of extra-cellular signaling, including the Wnt pathway, which is modulated by specific genetic variants. Overall, this study shows that genetic background plays a dominant role in driving phenotypic variability of PSCs.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Células-Tronco Pluripotentes / Células-Tronco Pluripotentes Induzidas Idioma: En Ano de publicação: 2020 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Células-Tronco Pluripotentes / Células-Tronco Pluripotentes Induzidas Idioma: En Ano de publicação: 2020 Tipo de documento: Article