Female human pluripotent stem cells rapidly lose X chromosome inactivation marks and progress to a skewed methylation pattern during culture

Molecular Human Reproduction
M GeensC Spits

Abstract

Does a preferential X chromosome inactivation (XCI) pattern exist in female human pluripotent stem cells (hPSCs) and does the pattern change during long-term culture or upon differentiation? We identified two independent phenomena that lead to aberrant XCI patterns in female hPSC: a rapid loss of histone H3 lysine 27 trimethylation (H3K27me3) and long non-coding X-inactive specific transcript (XIST) expression during culture, often accompanied by erosion of XCI-specific methylation, and a frequent loss of random XCI in the cultures. Variable XCI patterns have been reported in female hPSC, not only between different hPSC lines, but also between sub-passages of the same cell line, however the reasons for this variability remain unknown. Moreover, while non-random XCI-linked DNA methylation patterns have been previously reported, their origin and extent have not been investigated. We investigated the XCI patterns in 23 human pluripotent stem cell (hPSC) lines, during long-term culture and after differentiation, by gene expression analysis, histone modification assessment and study of DNA methylation. The presence and location of H3K27me3 was studied by immunofluorescence, XIST expression by real-time PCR, and mono- or bi-allelic e...Continue Reading

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Citations

Jan 24, 2017·The Keio Journal of Medicine·Tomoko Andoh-NodaHideyuki Okano
Mar 20, 2018·F1000Research·Joke TerrynCatherine Verfaillie
May 16, 2019·The EMBO Journal·Shiran Bar, Nissim Benvenisty
Jun 6, 2017·Human Reproduction Update·Mieke Geens, Susana M Chuva De Sousa Lopes
Mar 22, 2019·Human Reproduction Open·C EguizabalA Veiga
Sep 14, 2021·Frontiers in Neuroscience·Florencia D HaaseWendy A Gold

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