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Title: Human naïve pluripotent stem cells exhibit X chromosome dampening and X-inactivation (single cell RNA-Seq)      
keywords:
Transcriptome or Gene expression
ID:
PRJNA343935
description:
Naïve human embryonic stem cells (hESCs) can be derived from primed hESCs or directly from blastocysts, but their X-chromosome state has remained unresolved. We found that the inactive X-chromosome (Xi) of primed hESCs was reactivated in naïve culture conditions. Similar to cells of the blastocyst, resulting naive cells exhibited two active X-chromosomes with XIST expression and chromosome-wide transcriptional dampening, and initiated XIST-mediated X-inactivation upon differentiation. Both establishment and exit from the naïve 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. Furthermore, the naïve state reset Xi abnormalities of primed hESCs, providing cells better suited for downstream applications. However, naïve hESCs displayed differences to the embryo because XIST expression was predominantly mono-allelic instead of bi-allelic, and X-inactivation was non-random, indicating the need for further culture improvement. Overall design: Differentiated naïve human embryonic stem cells and naïve human embryonic stem cells at different passages (Exp1 for late passage, Exp2 for early passage) were subjected to single cell RNA sequencing by the Fluidigm C1 Single-Cell Auto Prep System.
accesstypes:
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landingpage: http://www.ncbi.nlm.nih.gov/bioproject/PRJNA343935
authentication:
none
authorization:
none
ID:
pmid:27989770
name:
Homo sapiens
ncbiID:
ncbitax:9606
abbreviation:
NCBI
homePage: http://www.ncbi.nlm.nih.gov
ID:
SCR:006472
name:
National Center for Biotechnology Information
homePage: http://www.ncbi.nlm.nih.gov/bioproject
ID:
SCR:004801
name:
NCBI BioProject
  • R01 MH104610/MH/NIMH NIH HHS/United States

  • F31 GM115122/GM/NIGMS NIH HHS/United States

  • R01 HD079546/HD/NICHD NIH HHS/United States

  • UL1 TR000124/TR/NCATS NIH HHS/United States

  • P01 GM099134/GM/NIGMS NIH HHS/United States

  • R01 NS088538/NS/NINDS NIH HHS/United States

  • R37 HD045022/HD/NICHD NIH HHS/United States

  • Wellcome Trust/United Kingdom

  • R01 CA084198/CA/NCI NIH HHS/United States

  • 098889/Z/12/Z/Wellcome Trust/United Kingdom

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