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Title: X chromosome reactivation dynamics reveal stages of reprogramming to pluripotency
Authors: Pasque, Vincent *
Tchieu, Jason *
Karnik, Rahul
Uyeda, Molly
Sadhu Dimashkie, Anupama
Case, Dana
Papp, Bernadett
Bonora, Giancarlo
Patel, Sanjeet
Ho, Ritchie
Schmidt, Ryan
McKee, Robin
Sado, Takashi
Tada, Takashi
Meissner, Alexander
Plath, Kathrin # ×
Issue Date: Dec-2014
Publisher: MIT Press
Series Title: Cell vol:159 issue:7 pages:1681-97
Article number: 10.1016/j.cell.2014.11.040
Abstract: Reprogramming to iPSCs resets the epigenome of somatic cells, including the reversal of X chromosome inactivation. We sought to gain insight into the steps underlying the reprogramming process by examining the means by which reprogramming leads to X chromosome reactivation (XCR). Analyzing single cells in situ, we found that hallmarks of the inactive X (Xi) change sequentially, providing a direct readout of reprogramming progression. Several epigenetic changes on the Xi occur in the inverse order of developmental X inactivation, whereas others are uncoupled from this sequence. Among the latter, DNA methylation has an extraordinary long persistence on the Xi during reprogramming, and, like Xist expression, is erased only after pluripotency genes are activated. Mechanistically, XCR requires both DNA demethylation and Xist silencing, ensuring that only cells undergoing faithful reprogramming initiate XCR. Our study defines the epigenetic state of multiple sequential reprogramming intermediates and establishes a paradigm for studying cell fate transitions during reprogramming.
URI: 
ISSN: 0092-8674
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Non-KU Leuven Association publications
* (joint) first author
× corresponding author
# (joint) last author

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