Generating a human Sertoli-like cell model from human terminal differentiated fibroblast-derived induced pluripotent stem cells.

Sertoli cells are main players in the male gonads development and their study may shed light on 46XY disorders on sex development. Unfortunately, mature primary Sertoli cells are incapable of proliferate in prolonged in vitro cultures and the available Sertoli cell models have several limitations since they derive from mouse or human cancer tissues. We differentiated human fibroblasts-derived induced pluripotent stem cells (iPSCs) into Sertoli-like cells (SLCs) and in order to characterize this new Sertoli cell model, we performed gene expression analyses by new generation sequencing techniques. This approach revealed that our putative Sertoli-like cells expressed Sertoli-cell markers such as SRY-Related HMG-Box 9 (SOX9), vimentin (VIM), and claudin-11 (CLDN-11). When compared with the actual models available (human NT2D1 and mouse TM4 cells), our Sertoli-like cells shown a reduction of germ cell markers (such as Sex Determining Region Y-Box 2 (SOX2), Octamer-Binding Protein 4 (OCT4), Developmental Pluripotency Associated 2 (DPPA2), Developmental Pluripotency Associated 4 (DPPA4) and Homeobox Transcription Factor Nanog (NANOG)) and an increased expression of immature Sertoli markers (e.g. Cytochrome P450 Retinoid Metabolizing Protein (CYP26B1) and Proto-Oncogene Tyrosine-Protein Kinase Src (SRC)). We additionally demonstrated the ability of our Sertoli-like cells to form three dimensional structures when growing in extracellular matrix gel. Harnessing the power of iPSCs we were able to generate Sertoli-like cells that show genetic and functional similarities to human Sertoli cells. SLCs can become an alternative source of Sertoli cells which could be of paramount benefit for both basic research and clinical applications, in sex development and reproductive medicine.