Comparable Frequencies of Coding Mutations and Loss of Imprinting in Human Pluripotent Cells Derived by Nuclear Transfer and Defined Factors

The recent finding that reprogrammed human pluripotent stem cells can be derived by nuclear transfer into human oocytes as well as by induced expression of defined factors has revitalized the debate on whether one approach might be advantageous over the other. Here we compare the genetic and epigenetic integrity of human nuclear-transfer embryonic stem cell (NT-ESC) lines and isogenic induced pluripotent stem cell (iPSC) lines, derived from the same somatic cell cultures of fetal, neonatal, and adult origin. The two cell types showed similar genome-wide gene expression and DNA methylation profiles. Importantly, NT-ESCs and iPSCs had comparable numbers of de novo coding mutations, but significantly more than parthenogenetic ESCs. As iPSCs, NT-ESCs displayed clone- and gene-specific aberrations in DNA methylation and allele-specific expression of imprinted genes. The occurrence of these genetic and epigenetic defects in both NT-ESCs and iPSCs suggests that they are inherent to reprogramming, regardless of derivation approach. [Display omitted] •Isogenic human NT-ESCs and iPSCs were derived from the same somatic cell cultures•Human NT-ESCs and iPSCs show similar profiles of gene expression and DNA methylation•De novo coding mutations occur at the same rate in human NT-ESC and iPSC lines•Loss of imprinting occurs in both NT-ESC and iPSC lines at similar frequencies Johannesson et al. compare human somatic cells reprogrammed to pluripotency via SCNT and as iPSCs. They find similar gene expression and DNA methylation profiles, as well as comparable levels of genomic aberrations such as coding mutations and imprinted gene expression defects. This suggests that neither reprogramming method is superior in this regard.