EGF and LIF enhanced the spontaneous reprogramming of Spermatogonial Stem Cells into Pluripotent State

Germline stem cells are unipotent stem cells dedicated to differentiate into gemmates throughout of life. However, spontaneous reprogramming of spermatogonial stem cells (SSCs) in long-term culture indicates the acquirement of pluripotency of germ cells affected by microenvironment.epidermal growth factor (EGF), leukemia inhibitory factor (LIF) and fresh mouse embryonic fibroblast (MEF) feeder are essential for transformation, and addition of 2i further enhanced the pluripotency. Transcriptome analysis revealed that EGF activated RAS signaling pathway and inhibited p38 to initiate transformation, and synergically cooperated with LIF to promote the transformation propensity. The increased efficiency of SSCs spontaneous reprogramming established new avenues for regenerative medicine, animal cloning, and research model for germline fate determination.