The dynamic changes of X chromosome inactivation during early culture of human embryonic stem cells.
X chromosome inactivation (XCI) is required for dosage compensation of X-linked genes in human female cells. Several previous reports have described the promiscuous XCI status in long-term cultured female human embryonic stem cells (hESCs), and the majority of them exhibit non-random XCI. However, when and how such female hESCs acquire the aberrant XCI states during culture is unknown. Herein, through comparing the XCI states in 18 paired hES cell lines throughout early culture, we revealed a uniform dynamic change during this culture period under a widely used culture condition. The female initial hESCs (ihESCs, P4-P9) expressed XIST RNA, H3K27me3 punctate enrichment and displayed random XCI pattern. By further culturing, the female early hESCs (ehESCs, P20-P30) lost the expression of XIST RNA, H3K27me3 punctate enrichment and exhibited a completely skewed XCI pattern. Importantly, a subset of X-linked genes was up-regulated in ehESCs, including some cancer-related genes. At last, we found 5% physiological oxygen was beneficial for the expression of XIST and H3K27me3 punctate enrichment, but not for the XCI pattern. We conclude that the XCI dynamic change is a frequent epigenetic instability event during early culture, which is accompanied by the up-regulation of some X-linked genes. Furthermore, we emphasize that physiological oxygen is beneficial for XCI fidelity.
['Xie|Pingyuan|P|', 'Ouyang|Qi|Q|', 'Leng|Lizhi|L|', 'Hu|Liang|L|', 'Cheng|Dehua|D|', 'Tan|Yueqiu|Y|', 'Lu|Guangxiu|G|', 'Lin|Ge|G|']
D002454:Cell Differentiation D002478:Cells, Cultured D019175:DNA Methylation D005260:Female D006657:Histones D000066449:Human Embryonic Stem Cells D006801:Humans D008856:Microscopy, Fluorescence D010100:Oxygen D011401:Promoter Regions, Genetic D062085:RNA, Long Noncoding D049951:X Chromosome Inactivation
X chromosome inactivation Human embryonic stem cells Epigenetics Culture alteration Gene expression regulation