Human Naive Pluripotent Stem Cells Model X Chromosome Dampening and X Inactivation
Author(s)
Sahakyan, Anna; Kim, Rachel; Chronis, Constantinos; Sabri, Shan; Bonora, Giancarlo; Theunissen, Thorold W.; Kuoy, Edward; Langerman, Justin; Clark, Amander T.; Plath, Kathrin; Jaenisch, Rudolf; ... Show more Show less
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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.
Date issued
2016-12Department
Massachusetts Institute of Technology. Department of BiologyJournal
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
ISSN
1934-5909