Female human iPS cells retain an inactive X-chromosome
Generating induced pluripotent stem cells (iPSCs) requires massive epigenome reorganization. It is unclear whether reprogramming of female human cells reactivates the inactive X chromosome (Xi), like in mouse. Here we establish that human (h)iPSCs derived from several female fibroblasts under standa...
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Published in | Cell stem cell Vol. 7; no. 3; pp. 329 - 342 |
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Main Authors | , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
19.08.2010
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Online Access | Get full text |
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Summary: | Generating induced pluripotent stem cells (iPSCs) requires massive epigenome reorganization. It is unclear whether reprogramming of female human cells reactivates the inactive X chromosome (Xi), like in mouse. Here we establish that human (h)iPSCs derived from several female fibroblasts under standard culture conditions carry an Xi. Despite the lack of reactivation, the Xi undergoes defined chromatin changes, and expansion of hiPSCs can lead to partial loss of
XIST
RNA. These results indicate that hiPSCs are epigenetically dynamic and do not display a pristine state of X-inactivation with two active X’s as found in some female human embryonic stem cells. Furthermore, while fibroblasts are mosaic for the Xi, hiPSCs are clonal for the Xi. This non-random pattern of X chromosome inactivation in female hiPSCs, which is maintained upon differentiation, has critical implications for clinical applications and disease modeling, and could be exploited for a unique form of gene therapy for X-linked diseases. |
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Bibliography: | these authors contributed equally to this work |
ISSN: | 1934-5909 1875-9777 |
DOI: | 10.1016/j.stem.2010.06.024 |