High-resolution chromosomal microarray analysis of early-stage human embryonic stem cells reveals an association between X chromosome instability and skewed X inactivationReportar como inadecuado




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Cell and Bioscience

, 4:74

First Online: 02 December 2014Received: 02 September 2014Accepted: 17 November 2014

Abstract

X chromosome inactivation XCI is a dosage compensation mechanism that silences the majority of genes on one X chromosome in each female cell via a random process. Skewed XCI is relevant to many diseases, but the mechanism leading to it remains unclear. Human embryonic stem cells hESCs derived from the inner cell mass ICM of blastocyst-stage embryos have provided an excellent model system for understanding XCI initiation and maintenance. Here, we derived hESC lines with random or skewed XCI patterns from poor-quality embryos and investigated the genome-wide copy number variation CNV and loss of heterozygosity LOH patterns at the early passages of these two groups of hESC lines. It was found that the average size of CNVs on the X chromosomes in the skewed group is twice as much as that in the random group. Moreover, the LOH regions of the skewed group covered the gene locus of either XIST or XACT, which are master long non-coding RNA lncRNA effectors of XCI in human pluripotent stem cells. In conclusion, our work has established an experimentally tractable hESC model for study of skewed XCI and revealed an association between X chromosome instability and skewed XCI.

KeywordsHuman embryonic stem cells Skewed X chromosome inactivation Chromosomal microarray analysis Genome instability AbbreviationsAFPA-fetoprotein

CMAChromosomal microarray analysis

CNVCopy number variation

EBEmbryonic body

hESCHuman embryonic stem cells

HUMARAHuman androgen-receptor gene

ICMInner cell mass

lncRNALong non-coding RNA

LOHLoss of heterozygosity

SMASmooth muscle actin

SNPSingle nucleotide polymorphism

STRShort tandem repeat

XACTX-active coating transcript

XCIX chromosome inactivation

XICX inactivation center

XISTX-inactive specific transcript.

Electronic supplementary materialThe online version of this article doi:10.1186-2045-3701-4-74 contains supplementary material, which is available to authorized users.

Yumei Luo, Jieliang Li, Detu Zhu contributed equally to this work.

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Autor: Yumei Luo - Jieliang Li - Detu Zhu - Yong Fan - Shaoying Li - Xiaofang Sun

Fuente: https://link.springer.com/



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