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The Capital Region of Denmark - a part of Copenhagen University Hospital
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An In Vitro Differentiation Protocol for Human Embryonic Bipotential Gonad and Testis Cell Development

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  • Ingrid M Knarston
  • Svenja Pachernegg
  • Gorjana Robevska
  • Irene Ghobrial
  • Pei Xuan Er
  • Elizabeth Georges
  • Minoru Takasato
  • Alexander N Combes
  • Anne Jørgensen
  • Melissa H Little
  • Andrew H Sinclair
  • Katie L Ayers
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Currently an in vitro model that fully recapitulates the human embryonic gonad is lacking. Here we describe a fully defined feeder-free protocol to generate early testis-like cells with the ability to be cultured as an organoid, from human induced pluripotent stem cells. This stepwise approach uses small molecules to mimic embryonic development, with upregulation of bipotential gonad markers (LHX9, EMX2, GATA4, and WT1) at day 10 of culture, followed by induction of testis Sertoli cell markers (SOX9, WT1, and AMH) by day 15. Aggregation into 3D structures and extended culture on Transwell filters yielded organoids with defined tissue structures and distinct Sertoli cell marker expression. These studies provide insight into human gonadal development, suggesting that a population of precursor cells may originate from a more lateral region of the mesoderm. Our protocol represents a significant advance toward generating a much-needed human gonad organoid for studying disorders/differences of sex development.

Original languageEnglish
JournalStem Cell Reviews and Reports
Volume15
Issue number6
Pages (from-to)1377-1391
Number of pages15
ISSN1550-8943
DOIs
Publication statusPublished - 8 Dec 2020

ID: 61412862