title: High-resolution chromosomal microarray analysis of early-stage human embryonic stem cells reveals an association between X chromosome instability and skewed X inactivation.
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.
authors.affiliation: Key Laboratory for Major Obstetric Diseases of Guangdong Province; Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, The Third Affiliated Hospital of Guangzhou Medical University, 63 Duobao Road, Liwan District, Guangzhou, Guangdong 510150 People's Republic of China.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Key Laboratory for Major Obstetric Diseases of Guangdong Province; Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, The Third Affiliated Hospital of Guangzhou Medical University, 63 Duobao Road, Liwan District, Guangzhou, Guangdong 510150 People's Republic of China.
authors.forename: Jieliang
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory for Major Obstetric Diseases of Guangdong Province; Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, The Third Affiliated Hospital of Guangzhou Medical University, 63 Duobao Road, Liwan District, Guangzhou, Guangdong 510150 People's Republic of China.
authors.forename: Detu
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Key Laboratory for Major Obstetric Diseases of Guangdong Province; Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, The Third Affiliated Hospital of Guangzhou Medical University, 63 Duobao Road, Liwan District, Guangzhou, Guangdong 510150 People's Republic of China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Key Laboratory for Major Obstetric Diseases of Guangdong Province; Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, The Third Affiliated Hospital of Guangzhou Medical University, 63 Duobao Road, Liwan District, Guangzhou, Guangdong 510150 People's Republic of China.
authors.forename: Shaoying
authors.initials: S
authors.lastname: Li
authors.affiliation: Key Laboratory for Major Obstetric Diseases of Guangdong Province; Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, The Third Affiliated Hospital of Guangzhou Medical University, 63 Duobao Road, Liwan District, Guangzhou, Guangdong 510150 People's Republic of China.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Sun
keywords: Chromosomal microarray analysis; Genome instability; Human embryonic stem cells; Skewed X chromosome inactivation