Human Naive Pluripotent Stem Cells Model X Chromosome Dampening and X Inactivation
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Author(s)
Sahakyan, Anna
Kim, Rachel
Chronis, Constantinos
Sabri, Shan
Bonora, Giancarlo
Theunissen, Thorold W.
Kuoy, Edward
Langerman, Justin
Clark, Amander T.
Plath, Kathrin
Date Issued
December 2016
Journal
Cell Stem Cell
Publisher
Elsevier
Citation
Sahakyan, Anna et al. “Human Naive Pluripotent Stem Cells Model X Chromosome Dampening and X Inactivation.” Cell Stem Cell 20, no. 1 (January 2017): 87–101 © 2017 The Authors
Version
Author's final manuscript
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 XaXaintermediate. 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 Xiabnormalities seen in primed hESCs, it may provide cells better suited for downstream applications.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/J.STEM.2016.10.006
