Targeted epigenetic reprogramming of endogenous loci by CRISPR/Cas9-based transcriptional activators directly converts fibroblasts to Leydig cells

Leydig cells (LC), which have exclusive function of synthesizing and secreting androgens, are considered as the major source of androgen in mature males. We hypothesize that the reprogramming of fibroblasts into Leydig cells is mediated by the epigenetic alterations in the nucleus which drives the stable expression of endogenous steroidogenic genes. We achieved the efficient reprogramming of skin fibroblasts into functional LCs using CRISPR/Cas9 with targeting genome editing and cell signaling mediators. The research will provide the foundation of stem cell therapy for male hypogonadism.