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

Ido Sagi, Joao C. De Pinho, Michael V. Zuccaro, Chen Atzmon, Tamar Golan-Lev, Ofra Yanuka, Robert Prosser, Alexandra Sadowy, Gloria Perez, Thiago Cabral, Benjamin Glaser, Stephen H. Tsang, Robin Goland, Mark V. Sauer, Rogerio Lobo, Nissim Benvenisty*, Dieter Egli

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

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.

Original languageAmerican English
Pages (from-to)419-432.e9
JournalCell Stem Cell
Volume25
Issue number3
DOIs
StatePublished - 5 Sep 2019

Bibliographical note

Publisher Copyright:
© 2019 Elsevier Inc.

Keywords

  • IGF2
  • androgenesis
  • differentiation bias
  • genomic imprinting
  • human embryonic stem cells
  • human pluripotent stem cells
  • parental imprinting
  • parthenogenesis

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