Stable X chromosome reactivation in female human induced pluripotent stem cells.

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 Reports

journal_title

Stem cell reports

authors

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 J

doi

10.1016/j.stemcr.2014.12.012

subject

Has Abstract

pub_date

2015-02-10 00:00:00

pages

199-208

issue

2

issn

2213-6711

pii

S2213-6711(15)00002-8

journal_volume

4

pub_type

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