A computational systems approach for identification of synergistic specification genes facilitates lineage conversion to prostate tissue

We report that a computational systems approach can identify cell type specification genes that act synergistically, and demonstrate its application for reprogramming of fibroblasts to prostate tissue. We have employed three such master regulators (FOXA1, NKX3.1, and androgen receptor, AR) in a primed conversion strategy to generate prostate tissue from mouse fibroblasts, involving expression of pluripotency factors, tissue recombination with embryonic urogenital mesenchyme, and renal grafting. Overall design: RNA-sequencing profiles of prostate tissues and fibroblasts were generated and compared to RNA-sequencing profiles of induced prostate tissue in tissue recombinants.