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

Giuliano Giuseppe Stirparo; Austin Smith; Ge Guo

doi:10.1016/j.stem.2020.11.014

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

Cell Stem Cell. 2021 Jan 7;28(1):164-169.e2. doi: 10.1016/j.stem.2020.11.014. Epub 2020 Dec 14.

Authors

Giuliano Giuseppe Stirparo¹, Austin Smith², Ge Guo³

Affiliations

¹ Wellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, CB2 0AW, UK; Living Systems Institute, University of Exeter, Exeter, EX4 4QD, UK.
² Wellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, CB2 0AW, UK; Living Systems Institute, University of Exeter, Exeter, EX4 4QD, UK; Department of Biochemistry, University of Cambridge, Cambridge, CB2 1QR, UK. Electronic address: austin.smith@exeter.ac.uk.
³ Wellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, CB2 0AW, UK; Living Systems Institute, University of Exeter, Exeter, EX4 4QD, UK. Electronic address: g.guo@exeter.ac.uk.

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.

Keywords: SNP; TP53; cancer-related mutations; genetic integrity; naive pluripotency; pluripotent stem cell; sequencing informatics; single nucleotide polymorphism.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Differentiation
Feeder Cells
Humans
Mice
Mutation / genetics
Neoplasms*
Pluripotent Stem Cells*
Sequence Analysis, RNA

Abstract

Publication types

MeSH terms

Grants and funding