UM
X-inactivation in female human embryonic stem cells is in a nonrandom pattern and prone to epigenetic alterations
Yin Shen1; Youko Matsuno4; Shaun D. Fouse1; Nagesh Rao2; Sierra Root5; Renhe Xu5; Matteo Pellegrini3; Arthur D. Riggs4; Guoping Fan1
2008-03-25
Source PublicationProceedings of the National Academy of Sciences of the United States of America
ISSN00278424 10916490
Volume105Issue:12Pages:4709-4714
Abstract

Xchromosome inactivation (XCI) is an essential mechanism for dosage compensation of X-linked genes in female cells. We report that subcultures from lines of female human embryonic stem cells (hESCs) exhibit variation (0-100%) for XCI markers, including XIST RNA expression and enrichment of histone H3 lysine 27 trimethylation (H3K27me3) on the inactive X chromosome (Xi). Surprisingly, regardless of the presence or absence of XCI markers in different cultures, all female hESCs we examined (H7, H9, and HSF6 cells) exhibit a monoallelic expression pattern for a majority of X-linked genes. Our results suggest that these established female hESCs have already completed XCI during the process of derivation and/or propagation, and the XCI pattern of lines we investigated is already not random. Moreover, XIST gene expression in subsets of cultured female hESCs is unstable and subject to stable epigenetic silencing by DNA methylation. In the absence of XIST expression, ≈12% of X-linked promoter CpG islands become hypomethylated and a portion of X-linked alleles on the Xi are reactivated. Because alterations in dosage compensation of X-linked genes could impair somatic cell function, wepropose that XCI status should be routinely checked in subcultures of female hESCs, with cultures displaying XCI markers better suited for use in regenerative medicine. © 2008 by The National Academy of Sciences of the USA.

KeywordCulture Variation Dna Methylation Gene Regulation
DOI10.1073/pnas.0712018105
URLView the original
Language英语
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000254772700033
PublisherNATL ACAD SCIENCES, 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
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Cited Times [WOS]:151   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Corresponding AuthorArthur D. Riggs; Guoping Fan
Affiliation1.Department of Human Genetics, Geffen School of Medicine,
2.Pathology and Laboratory Medicine
3.Molecular Cell and Developmental Biology, University of California, Los Angeles, CA 90095
4.Division of Biology, Beckman Research Institute of the City of Hope, Duarte, CA 91010
5.Department of Genetics and Development, University of Connecticut Health Center, Farmington, CT 06032
Recommended Citation
GB/T 7714
Yin Shen,Youko Matsuno,Shaun D. Fouse,et al. X-inactivation in female human embryonic stem cells is in a nonrandom pattern and prone to epigenetic alterations[J]. Proceedings of the National Academy of Sciences of the United States of America,2008,105(12):4709-4714.
APA Yin Shen.,Youko Matsuno.,Shaun D. Fouse.,Nagesh Rao.,Sierra Root.,...&Guoping Fan.(2008).X-inactivation in female human embryonic stem cells is in a nonrandom pattern and prone to epigenetic alterations.Proceedings of the National Academy of Sciences of the United States of America,105(12),4709-4714.
MLA Yin Shen,et al."X-inactivation in female human embryonic stem cells is in a nonrandom pattern and prone to epigenetic alterations".Proceedings of the National Academy of Sciences of the United States of America 105.12(2008):4709-4714.
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