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February 21, 2023
Publications › Directed differentiation of human iPSCs to functional ovarian granulosa-like cells via transcription factor overexpression

Study demonstrates the generation of ovarian support cells (OSCs) from hiPSCs through the induced expression of specific transcription factors

Study conducted in partnership with the George Church Lab at The Wyss Institute of Harvard Medical School describes a novel protocol to generate granulosa-like cells through targeted transcription factor overexpression.

Findings

  • Overexpression of transcription factors NR5A1 and either RUNX1 or RUNX2 is sufficient to generate granulosa-like cells
  • Generated granulosa-like cells have transcriptomes similar to human fetal ovarian cells and recapitulate key ovarian phenotypes, including follicle formation and steroidogenesis
  • When aggregated with hPGCLCs, generated cells form ovary-like organoids (ovaroids) and support human primordial germ cell-like cells (hPGCLC) development from the premigratory to the gonadal stage as measured by induction of DAZL expression

Clinical Significance

This model system will provide unique opportunities for studying human ovarian biology and may enable the development of therapies for female reproductive health.

  • Granulosa-like cells can be used to improve fertility treatments (see Human-induced pluripotent stem cell-derived ovarian support cell co-culture improves oocyte maturation in vitro after abbreviated gonadotropin stimulation)
  • Currently used animal models are insufficient to study the female reproductive system as they do not experience menstruation, menopause, or common female reproductive diseases
  • Ovaroids may be used for disease modeling, predictive drug development, and more

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