The consequences of recurrent genetic and epigenetic variants in human pluripotent stem cells.

Document Type

Article

Publication Date

12-1-2022

Publication Title

Cell Stem Cell

Keywords

JMG, Humans, Epigenomics, Pluripotent Stem Cells, Stem Cell Research, Oncogenes, Epigenesis, Genetic

JAX Source

Cell Stem Cell. 2022;29(12):1624-36

Volume

29

Issue

12

First Page

1624

Last Page

1636

ISSN

1875-9777

PMID

36459966

DOI

https://doi.org/10.1016/j.stem.2022.11.006

Abstract

It is well established that human pluripotent stem cells (hPSCs) can acquire genetic and epigenetic changes during culture in vitro. Given the increasing use of hPSCs in research and therapy and the vast expansion in the number of hPSC lines available for researchers, the International Society for Stem Cell Research has recognized the need to reassess quality control standards for ensuring the genetic integrity of hPSCs. Here, we summarize current knowledge of the nature of recurrent genetic and epigenetic variants in hPSC culture, the methods for their detection, and what is known concerning their effects on cell behavior in vitro or in vivo. We argue that the potential consequences of low-level contamination of cell therapy products with cells bearing oncogenic variants are essentially unknown at present. We highlight the key challenges facing the field with particular reference to safety assessment of hPSC-derived cellular therapeutics.

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