摘要：SummaryInduced 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 doin vivo.Graphical abstractDisplay OmittedHighlights•Shared mutations in fetal cells allow pre-gastrulation mutation rate estimation•Human pluripotent cells have anin vivomutation rate of 1.65 mutations per division•iPSCs generated from fetal cells show a similar mutation rate in hypoxic conditions•Similar mutational processes are active in iPSCs and pre-gastrulation embryonic cellsCell biology; Genomics; Stem cells research
