Conversion of human fibroblasts into functional Leydig-like cells by small molecules and a single factor

Abstract

Reprogramming fibroblasts into Leydig cells (LCs) offers a promising source for cell-based therapy for male hypogonadism. Recently, it has been achieved by forced expression of multiple transcription factors (TFs). However, for ultimate safe and convenient application, small molecules would be a revolutionary and desirable method to reduce or eliminate the genetic manipulations. Here, we report a defined small-molecule cocktail that enables the highly efficient conversion of human fibroblasts into functional LCs with only one transcription factor. These induced cells resembled human LCs with respect to morphology, marker gene expression and secretary function of testosterone. This study lays a foundation for future pharmacological reprogramming and provides a unique venue for investigating mechanisms underlying reprogramming.

Keywords: Cell-based therapy; Conversion; Leydig cell; Reprogramming; Small molecule.