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Erosion of dosage compensation impacts human iPSC disease modeling.

Abstract：

:Although distinct human induced pluripotent stem cell (hiPSC) lines can display considerable epigenetic variation, it has been unclear whether such variability impacts their utility for disease modeling. Here, we show that although low-passage female hiPSCs retain the inactive X chromosome of the somatic cell they are derived from, over time in culture they undergo an "erosion" of X chromosome inactivation (XCI). This erosion of XCI is characterized by loss of XIST expression and foci of H3-K27-trimethylation, as well as transcriptional derepression of genes on the inactive X that cannot be reversed by either differentiation or further reprogramming. We specifically demonstrate that erosion of XCI has a significant impact on the use of female hiPSCs for modeling Lesch-Nyhan syndrome. However, our finding that most genes subject to XCI are derepressed by this erosion of XCI suggests that it should be a significant consideration when selecting hiPSC lines for modeling any disease.

journal_name

Cell Stem Cell

journal_title

Cell stem cell

authors

Mekhoubad S,Bock C,de Boer AS,Kiskinis E,Meissner A,Eggan K

doi

10.1016/j.stem.2012.02.014

subject

Has Abstract

pub_date

2012-05-04 00:00:00

pages

595-609

issue

5

eissn

1934-5909

issn

1875-9777

pii

S1934-5909(12)00073-2

journal_volume

10

pub_type

杂志文章

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