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Cancer-Related Mutations Are Not Enriched in Naive Human Pluripotent Stem Cells.

ABSTRACT: Previous analysis of RNA sequencing (RNA-seq) data from human naive pluripotent stem cells reported multiple point "mutations" in cancer-related genes and implicated selective culture conditions. We observed, however, that those mutations were only present in co-cultures with mouse feeder cells. Inspection of reads containing the polymorphisms revealed complete identity to the mouse reference genome. After we filtered reads to remove sequences of mouse origin, the actual incidence of oncogenic polymorphisms arising in naive pluripotent stem cells is close to zero.

SUBMITTER: Stirparo GG

PROVIDER: S-EPMC7837212 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:A recent paper reported multiple oncogenic point mutations in naïve human pluripotent stem cells (hPSC) and implicated selective culture conditions. However, we observed that those “polymorphisms” are only found when naïve hPSCs are co-cultured with mouse feeder cells. Inspection of the reads containing the reported mutations revealed that they are identical to mouse sequences. Filtering the data sets to remove reads contributed by mouse feeder cells reveals that the actual incidence of cancer-related polymorphisms is close to zero. Therefore, culture conditions for naïve hPSCs do not select for tumorigenic point mutations.

2020-11-30 | GSE150933 | GEO

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Project description:Cancer-Related Mutations are Not Enriched in Naïve Human Pluripotent Stem Cells

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Project description: Not available

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Epigenetic dynamics during capacitation of naive human pluripotent stem cells.

Project description:Human pluripotent stem cells (hPSCs) are of fundamental relevance in regenerative medicine. Naïve hPSCs hold promise to overcome some of the limitations of conventional (primed) hPSCs, including recurrent epigenetic anomalies. Naïve-to-primed transition (capacitation) follows transcriptional dynamics of human embryonic epiblast and is necessary for somatic differentiation from naïve hPSCs. We found that capacitated hPSCs are transcriptionally closer to postimplantation epiblast than conventional hPSCs. This prompted us to comprehensively study epigenetic and related transcriptional changes during capacitation. Our results show that CpG islands, gene regulatory elements, and retrotransposons are hotspots of epigenetic dynamics during capacitation and indicate possible distinct roles of specific epigenetic modifications in gene expression control between naïve and primed hPSCs. Unexpectedly, PRC2 activity appeared to be dispensable for the capacitation. We find that capacitated hPSCs acquire an epigenetic state similar to conventional hPSCs. Significantly, however, the X chromosome erosion frequently observed in conventional female hPSCs is reversed by resetting and subsequent capacitation.

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