Human induced pluripotent stem cells display a similar mutation burden as embryonic pluripotent cells in vivo

Karlijn A L Hasaart, Freek Manders, Joske Ubels, Mark Verheul, Markus J van Roosmalen, Niels M Groenen, Rurika Oka, Ewart Kuijk, Susana M Chuva de Sousa Lopes, Ruben van Boxtel

Research output: Contribution to journalArticlepeer-review

Abstract

Induced pluripotent stem cells (iPSCs) hold great promise for regenerative medicine, but genetic instability is a major concern. Embryonic pluripotent cells also accumulate mutations during early development, but how this relates to the mutation burden in iPSCs remains unknown. Here, we directly compared the mutation burden of cultured iPSCs with their isogenic embryonic cells during human embryogenesis. We generated developmental lineage trees of human fetuses by phylogenetic inference from somatic mutations in the genomes of multiple stem cells, which were derived from different germ layers. Using this approach, we characterized the mutations acquired pre-gastrulation and found a rate of 1.65 mutations per cell division. When cultured in hypoxic conditions, iPSCs generated from fetal stem cells of the assessed fetuses displayed a similar mutation rate and spectrum. Our results show that iPSCs maintain a genomic integrity during culture at a similar degree as their pluripotent counterparts do in vivo.

Original languageEnglish
Pages (from-to)103736
JournaliScience
Volume25
Issue number2
DOIs
Publication statusPublished - 18 Feb 2022

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