Transcriptomic landscape reveals germline potential of porcine skin-derived multipotent dermal fibroblast progenitors

Abstract According to estimations, approximately about 15% of couples worldwide suffer from infertility, in which individuals with azoospermia or oocyte abnormalities cannot be treated with assisted reproductive technology. The skin-derived stem cells (SDSC) differentiation into primordial germ cell-like cells (PGCLC) is one of the major breakthroughs in the field of stem cell intervention for infertility treatment in recent years. However, the cellular origin of SDSC and its dynamic changes in transcription profile during differentiation into PGCLC in vitro remain largely undissected. Here, the results of single-cell RNA sequencing indicated that porcine SDSC is mainly derived from multipotent dermal fibroblast progenitors (MDFP), which are regulated by growth factors (EGF/bFGF). Importantly, porcine SDSC exhibit pluripotency for differentiating into three germ layers and can effectively differentiate into PGCLC through complex transcriptional regulation involving histone modification. Moreover, this study also highlights that porcine SDSC-derived PGCLC specification exhibit conservation with the human primordial germ cells lineage and that its proliferation is mediated by the MAPK signalling pathway. Our findings provide substantial novel insights into the field of regenerative medicine in which stem cells differentiate into germ cells in vitro, as well as potential therapeutic effects in individuals with azoospermia and/or defective oocytes.