PhD Candidate Amsterdam University Medical Centre (AMC), Netherlands
Abstract: Sertoli cells (SCs) play a crucial role in testicular development and spermatogenesis, providing structural and biochemical support to developing germ cells. However, limited access to human fetal testicular tissue limits our understanding of SC function and their role in germ cell maturation. In vitro gametogenesis (IVG) presents a promising approach to overcoming this challenge. Still current models depend on co-culture of germ cells with fetal or rodent somatic cells, and are therefore practically challenging or impedes proper translation to human, respectively. In addition, achieving full meiotic progression remains challenging. In this study, we aim to generate and characterize Sertoli-like cells (SLCs) from human-induced pluripotent stem cells (hiPSCs) to develop a human-derived testicular soma for IVG. Using directed differentiation, 2 hiPSC lines were induced through an intermediate mesodermal lineage and further differentiated into SLCs using FGF9, PGD2, and Activin A. Molecular analyses of the derived SLCs confirmed the upregulation of key SC markers (SOX9, WT1, VIM, AR), downregulation of pluripotency genes (NANOG, OCT3/4), thereby validating lineage commitment. Additional functional assessment through a fluorescent bead uptake assay demonstrated phagocytic activity, a defining feature of SCs in clearing apoptotic germ cells. These results establish a foundation for generating human SLCs in vitro, providing a relevant model to support germ cell maturation. This work advances the field by contributing to a fully humanized IVG system, with implications for fertility research and potential therapeutic applications in male infertility.
Funding Source: Funding for this work was provided via ZonMW PSIDER program no 10250022120001 (HipGametes)
