Differentiation of uniparental human embryonic stem cells into granulosa cells reveals a paternal contribution to gonadal development

Gal Keshet*, Shiran Bar, Roni Sarel-Gallily, Ofra Yanuka, Nissim Benvenisty*, Talia Eldar-Geva*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Genomic imprinting underlies the mammalian requirement for sexual reproduction. Nonetheless, the relative contribution of the two parental genomes during human development is not fully understood. Specifically, a fascinating question is whether the formation of the gonad, which holds the ability to reproduce, depends on equal contribution from both parental genomes. Here, we differentiated androgenetic and parthenogenetic human pluripotent stem cells (hPSCs) into ovarian granulosa-like cells (GLCs). We show that in contrast to biparental and androgenetic cells, parthenogenetic hPSCs present a reduced capacity to differentiate into GLCs. We further identify the paternally expressed gene IGF2 as the most upregulated imprinted gene upon differentiation. Remarkably, while IGF2 knockout androgenetic cells fail to differentiate into GLCs, the differentiation of parthenogenetic cells supplemented with IGF2 is partly rescued. Thus, our findings unravel a surprising essentiality of genes that are only expressed from the paternal genome to the development of the female reproductive system.

Original languageAmerican English
Pages (from-to)817-828
Number of pages12
JournalStem Cell Reports
Volume18
Issue number4
DOIs
StatePublished - 11 Apr 2023

Bibliographical note

Publisher Copyright:
© 2023 The Author(s)

Keywords

  • Androgenesis
  • Epigenetics
  • Genomic imprinting
  • Gonadal development
  • Granulosa
  • Human pluripotent stem cells
  • Parthenogenesis

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