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

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. Ins...

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Bibliographic Details
Published inCell stem cell Vol. 28; no. 1; pp. 164 - 169.e2
Main Authors Stirparo, Giuliano Giuseppe, Smith, Austin, Guo, Ge
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 07.01.2021
Cell Press
Subjects
Animals
cancer-related mutations
Cell Differentiation
Feeder Cells
genetic integrity
Humans
Matters Arising
Mice
Mutation - genetics
naive pluripotency
Neoplasms
pluripotent stem cell
Pluripotent Stem Cells
Sequence Analysis, RNA
sequencing informatics
single nucleotide polymorphism
SNP
TP53
SNP
single nucleotide polymorphism
pluripotent stem cell
cancer-related mutations
sequencing informatics
naive pluripotency
TP53
genetic integrity
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Summary: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. •Culture conditions for naive stem cells do not select for cancer-related mutations•Contaminating sequences in RNA-seq data can be misidentified as point mutations•Filtering to remove mouse sequences eliminates most mutations•Remaining mutations in naive stem cells are carried over from primed stem cells Acquisition of pathogenic mutations during in vitro propagation is a concern for applications of pluripotent stem cells. In this paper, Stirparo and colleagues show that detection of multiple mutations in naïve stem cells by RNA-seq analysis is due to contamination with mouse sequences. The actual cancer mutation incidence is low.
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ISSN:1934-5909
1875-9777
DOI:10.1016/j.stem.2020.11.014