Comparable frequencies of coding mutations and loss of imprinting in human pluripotent cells derived by nuclear transfer and defined factors

Cell Stem Cell. 2014 Nov 6;15(5):634-42. doi: 10.1016/j.stem.2014.10.002. Epub 2014 Nov 6.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Base Sequence
  • Clone Cells
  • DNA Methylation / genetics
  • Gene Expression Regulation
  • Genetic Loci
  • Genomic Imprinting / genetics*
  • Humans
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / metabolism
  • Male
  • Molecular Sequence Data
  • Mutation Rate*
  • Nuclear Transfer Techniques*
  • Open Reading Frames / genetics*
  • Pluripotent Stem Cells / cytology*
  • Pluripotent Stem Cells / metabolism

Associated data

  • GDB/GSE61657
  • GEO/GSE28024
  • GEO/GSE42077