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A viral transduction approach for iPSC differentiation into cortisol-producing steroidogenic cells

Lee-Glover, L. P.; Shutt, T. E.

2025-02-17 developmental biology
10.1101/2025.02.13.638168 bioRxiv
Show abstract

Steroid hormones are important signaling molecules that are primarily produced by specialized cells. The ability to culture steroidogenic cells is critical to study this important process. While a few steroidogenic cell lines are available for study, they are typically derived from cancer patients and do not reflect genetic alterations in steroidogenic genes that cause human disease. In this regard, iPSCs are a powerful tool for modeling human disease, as patient-derived iPSCs can be differentiated into a variety of different cell types. While other approaches exist to differentiate iPSCs into steroidogenic cells, they are typically complex and time consuming. In contrast, a simple approach based on lentivirus transduction of SF1, the master regulator of steroidogenesis, can differentiate multiple types of cultured cells into a steroidogenic state. However, we show here that this approach does not work for iPSCs. To circumvent this limitation, we report a simple adaptation that first differentiates iPSCs to embryoid bodies prior of SF1 transduction. With this modified approach, we provide a straightforward cost-effective approach to differentiate iPSCs into actively steroidogenic cells.

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