Culture-induced recurrent epigenetic aberrations in human pluripotent stem cells

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hPSCs were shown to acquire genetic aberrations during their growth in culture. The aberrations are non-random and positively selected, by altering multiple cellular phenotypes. Similarly to genetic mutations, epigenetic aberrations may also change gene expression levels, leading to altered cellular behaviors, as seen in tumors. In this study we focus on methylation changes, and we showed that there is a set of genes which are recurrently hypermethylated and silenced in high passage cells. One of these genes, TSPYL5, was shown to be downregulated by hypermethylation in multiple cancer types. We showed that upon its silencing in hPSC, differentiation genes and tumor-suppressor genes are downregulated, and pluripotency- and growth promoting genes are upregulated, which drive the positive selection. These results highlight another challenge faced by hPSC in regard to maintenance of intact gene expression program, and emphasize the role of epimutations described in cancer cells also to hPSCs.

Vyšlo v časopise: Culture-induced recurrent epigenetic aberrations in human pluripotent stem cells. PLoS Genet 13(8): e32767. doi:10.1371/journal.pgen.1006979
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1006979

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