Abstract:
:In placental mammals, balanced expression of X-linked genes is accomplished by X chromosome inactivation (XCI) in female cells. In humans, random XCI is initiated early during embryonic development. To investigate whether reprogramming of female human fibroblasts into induced pluripotent stem cells (iPSCs) leads to reactivation of the inactive X chromosome (Xi), we have generated iPSC lines from fibroblasts heterozygous for large X-chromosomal deletions. These fibroblasts show completely skewed XCI of the mutated X chromosome, enabling monitoring of X chromosome reactivation (XCR) and XCI using allele-specific single-cell expression analysis. This approach revealed that XCR is robust under standard culture conditions, but does not prevent reinitiation of XCI, resulting in a mixed population of cells with either two active X chromosomes (Xas) or one Xa and one Xi. This mixed population of XaXa and XaXi cells is stabilized in naive human stem cell medium, allowing expansion of clones with two Xas.
journal_name
Stem Cell Reportsjournal_title
Stem cell reportsauthors
Barakat TS,Ghazvini M,de Hoon B,Li T,Eussen B,Douben H,van der Linden R,van der Stap N,Boter M,Laven JS,Galjaard RJ,Grootegoed JA,de Klein A,Gribnau Jdoi
10.1016/j.stemcr.2014.12.012subject
Has Abstractpub_date
2015-02-10 00:00:00pages
199-208issue
2issn
2213-6711pii
S2213-6711(15)00002-8journal_volume
4pub_type
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