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Human Naive Pluripotent Stem Cells Model X Chromosome Dampening and X Inactivation.
Sahakyan, Anna; Kim, Rachel; Chronis, Constantinos; Sabri, Shan; Bonora, Giancarlo; Theunissen, Thorold W; Kuoy, Edward; Langerman, Justin; Clark, Amander T; Jaenisch, Rudolf; Plath, Kathrin.
Afiliação
  • Sahakyan A; Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Kim R; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Chronis C; Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Sabri S; Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Bioinformatics Interdepartmental Program, University
  • Bonora G; Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA; Bioinformatics Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Theunissen TW; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
  • Kuoy E; Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Langerman J; Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Clark AT; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, David Geffen School of
  • Jaenisch R; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
  • Plath K; Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California
Cell Stem Cell ; 20(1): 87-101, 2017 01 05.
Article em En | MEDLINE | ID: mdl-27989770
ABSTRACT
Naive human embryonic stem cells (hESCs) can be derived from primed hESCs or directly from blastocysts, but their X chromosome state has remained unresolved. Here, we show that the inactive X chromosome (Xi) of primed hESCs was reactivated in naive culture conditions. Like cells of the blastocyst, the resulting naive cells contained two active X chromosomes with XIST expression and chromosome-wide transcriptional dampening and initiated XIST-mediated X inactivation upon differentiation. Both establishment of and exit from the naive state (differentiation) happened via an XIST-negative XaXa intermediate. Together, these findings identify a cell culture system for functionally exploring the two X chromosome dosage compensation processes in early human development X dampening and X inactivation. However, remaining differences between naive hESCs and embryonic cells related to mono-allelic XIST expression and non-random X inactivation highlight the need for further culture improvement. As the naive state resets Xi abnormalities seen in primed hESCs, it may provide cells better suited for downstream applications.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Cromossomos Humanos X / Células-Tronco Pluripotentes / Inativação do Cromossomo X Tipo de estudo: Prognostic_studies Limite: Female / Humans Idioma: En Revista: Cell Stem Cell Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Estados Unidos
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Cromossomos Humanos X / Células-Tronco Pluripotentes / Inativação do Cromossomo X Tipo de estudo: Prognostic_studies Limite: Female / Humans Idioma: En Revista: Cell Stem Cell Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Estados Unidos