The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
Erosion of Dosage Compensation Impacts Human iPSC Disease Modeling
Open accessAbstract
Summary Although distinct human induced pluripotent stem cell (hiPSC) lines can display considerable epigenetic variation, it has been unclear if such variability impacts their utility for disease modeling. Here, we show that although low passage female hiPSCs retain the inactive X-chromosome of the somatic cell they are derived from, over time in culture they undergo an “erosion” of X-chromosome inactivation (XCI). This erosion of XCI is characterized by loss of XIST expression and foci of H3-K27-trimethylation, as well as transcriptional de-repression of genes on the inactive X that cannot be reversed by either differentiation or further reprogramming. We specifically demonstrate that erosion of XCI has a significant impact on the use of female hiPSCs for modeling Lesch-Nyhan syndrome. However, our finding that most genes subject to XCI are de-repressed by this erosion of XCI suggests that it should be a significant consideration when selecting hiPSC lines for modeling any disease.
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Cites
Somatic coding mutations in human induced pluripotent stem cells
Gore, A., Li, Z., Fung, H.-L., Young, J. E., Agarwal, S., Antosiewicz-Bourget, J., Canto, I., Giorgetti, A., Israel, M. A., Kiskinis, E., et al. (2011) · Nature · doi:10.1038/nature09805 · Cited by 1,273
Self-citationCheung, A. Y. L., Horvath, L. M., Grafodatskaya, D., Pasceri, P., Weksberg, R., Hotta, A., Carrel, L., & Ellis, J. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr093 · Cited by 271
Cited by
Rapid single-step induction of functional neurons from human pluripotent stem cells
Zhang, Y., Pak, C., Han, Y., Ahlenius, H., Zhang, Z., Chanda, S., Marro, S., Patzke, C., Acuna, C., Covy, J., et al. (2013) · Neuron · doi:10.1016/j.neuron.2013.05.029 · Cited by 1,644
Dynamic stem cell states: Naive to primed pluripotency in rodents and humans
Weinberger, L., Ayyash, M., Novershtern, N., & Hanna, J. H. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2015.28 · Cited by 622
Volpato, V., & Webber, C. (2020) · Disease Models & Mechanisms · doi:10.1242/dmm.042317 · Cited by 379
Genetic and Epigenetic Variations in iPSCs: Potential Causes and Implications for Application
Liang, G., & Zhang, Y. (2013) · Cell Stem Cell · doi:10.1016/j.stem.2013.07.001 · Cited by 369
Epigenetic resetting of human pluripotency
Guo, G., von Meyenn, F., Rostovskaya, M., Clarke, J., Dietmann, S., Baker, D., Sahakyan, A., Myers, S., Bertone, P., Reik, W., et al. (2017) · Development · doi:10.1242/dev.146811 · Cited by 319
Metadata
- Authors
- Mekhoubad, S., Bock, C., de Boer, A. S., Kiskinis, E., Meissner, A., & Eggan, K.
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2012-05
- Volume
- 10
- Issue
- 5
- Pages
- 595-609
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- OpenAlex
- W2041118365
- Cited by
- 360
- References
- 2
- FWCI
- 13.82
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Mekhoubad, S., Bock, C., de Boer, A. S., Kiskinis, E., Meissner, A., & Eggan, K. (2012). Erosion of Dosage Compensation Impacts Human iPSC Disease Modeling. Cell Stem Cell. https://doi.org/10.1016/j.stem.2012.02.014
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