Direct conversion of human fibroblasts into functional Leydig-like cells by SF-1 , GATA4 and NGFI-B .

The reprogramming of fibroblasts to induced pluripotent stem cells raises the possibility that a somatic cell can be reprogrammed to an alternative, differentiated fate without first becoming a stem/progenitor cell. Recent work has shown that fibroblasts can be reprogrammed to other, terminally differentiated cells with a combination of several transcription factors. Here, we report that a combination of four developmental transcription factors; , , , and ; efficiently reprogrammed human foreskin fibroblasts into functional induced Leydig-like cells (iLCs). The iLCs expressed Leydig-specific markers and secreted testosterone . We found that and were particularly critical for Leydig-specific markers expression and that , , and were necessary to generate functional iLCs that secreted testosterone. These findings demonstrate that fibroblasts can be directly converted into iLCs with a few, defined factors and may provide insight into potential therapies to treat testosterone deficiency.