دورية أكاديمية
Naive Pluripotent Stem Cells Exhibit Phenotypic Variability that Is Driven by Genetic Variation.
العنوان: | Naive Pluripotent Stem Cells Exhibit Phenotypic Variability that Is Driven by Genetic Variation. |
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المؤلفون: | 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, Germany., 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. |
المصدر: | Cell stem cell [Cell Stem Cell] 2020 Sep 03; Vol. 27 (3), pp. 470-481.e6. Date of Electronic Publication: 2020 Aug 13. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 101311472 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1875-9777 (Electronic) Linking ISSN: 18759777 NLM ISO Abbreviation: Cell Stem Cell Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Cambridge, MA : Cell Press |
مواضيع طبية MeSH: | Induced Pluripotent Stem Cells* , Pluripotent Stem Cells*, Animals ; Biological Variation, Population ; Cell Differentiation/genetics ; Genetic Variation ; Mice ; Reproducibility of Results |
مستخلص: | 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. Competing Interests: Declaration of Interests The authors declare no competing interests. (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.) |
التعليقات: | Comment in: Cell Stem Cell. 2020 Sep 3;27(3):347-349. (PMID: 32888420) |
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معلومات مُعتمدة: | MC_PC_17230 United Kingdom MRC_ Medical Research Council; MC_PC_12009 United Kingdom MRC_ Medical Research Council; NC/T2T0419 United Kingdom NC3RS_ National Centre for the Replacement, Refinement and Reduction of Animals in Research; R35 GM133495 United States GM NIGMS NIH HHS; U42 OD010921 United States OD NIH HHS; United Kingdom WT_ Wellcome Trust; NC/N001540/1 United Kingdom NC3RS_ National Centre for the Replacement, Refinement and Reduction of Animals in Research; G0701448 United Kingdom MRC_ Medical Research Council; P40 OD011102 United States OD NIH HHS |
فهرسة مساهمة: | Keywords: differentiation; eQTL; genetics; ground state; mouse embryonic stem cells; naïve; pluripotent stem cells; signaling; variability |
تواريخ الأحداث: | Date Created: 20200816 Date Completed: 20210423 Latest Revision: 20240429 |
رمز التحديث: | 20240429 |
مُعرف محوري في PubMed: | PMC7487768 |
DOI: | 10.1016/j.stem.2020.07.019 |
PMID: | 32795399 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1875-9777 |
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DOI: | 10.1016/j.stem.2020.07.019 |