Distinct Imprinting Signatures and Biased Differentiation of Human Androgenetic and Parthenogenetic Embryonic Stem Cells

Cell Stem Cell. 2019 Sep 5;25(3):419-432.e9. doi: 10.1016/j.stem.2019.06.013.


Genomic imprinting is an epigenetic mechanism that results in parent-of-origin monoallelic expression of specific genes, which precludes uniparental development and underlies various diseases. Here, we explored molecular and developmental aspects of imprinting in humans by generating exclusively paternal human androgenetic embryonic stem cells (aESCs) and comparing them with exclusively maternal parthenogenetic ESCs (pESCs) and bi-parental ESCs, establishing a pluripotent cell system of distinct parental backgrounds. Analyzing the transcriptomes and methylomes of human aESCs, pESCs, and bi-parental ESCs enabled the characterization of regulatory relations at known imprinted regions and uncovered imprinted gene candidates within and outside known imprinted regions. Investigating the consequences of uniparental differentiation, we showed the known paternal-genome preference for placental contribution, revealed a similar bias toward liver differentiation, and implicated the involvement of the imprinted gene IGF2 in this process. Our results demonstrate the utility of parent-specific human ESCs for dissecting the role of imprinting in human development and disease.

Keywords: IGF2; androgenesis; differentiation bias; genomic imprinting; human embryonic stem cells; human pluripotent stem cells; parental imprinting; parthenogenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cell Differentiation
  • Cells, Cultured
  • DNA Methylation
  • Embryonic Stem Cells / physiology*
  • Epigenesis, Genetic
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Genomic Imprinting
  • Humans
  • Insulin-Like Growth Factor II / genetics
  • Male
  • Parents
  • Parthenogenesis / physiology*
  • Pluripotent Stem Cells / physiology*
  • Sex Characteristics*
  • Transcriptome


  • IGF2 protein, human
  • Insulin-Like Growth Factor II