TY - JOUR
T1 - Human induced pluripotent stem cells display a similar mutation burden as embryonic pluripotent cells in vivo
AU - Hasaart, Karlijn A L
AU - Manders, Freek
AU - Ubels, Joske
AU - Verheul, Mark
AU - van Roosmalen, Markus J
AU - Groenen, Niels M
AU - Oka, Rurika
AU - Kuijk, Ewart
AU - Lopes, Susana M Chuva de Sousa
AU - Boxtel, Ruben van
N1 - © 2022 The Authors.
PY - 2022/2/18
Y1 - 2022/2/18
N2 - 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.
AB - 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.
U2 - 10.1016/j.isci.2022.103736
DO - 10.1016/j.isci.2022.103736
M3 - Article
C2 - 35118356
VL - 25
SP - 103736
JO - iScience
JF - iScience
SN - 2589-0042
IS - 2
ER -