Potency of germ cells and its relevance for regenerative medicine

Abstract

Germline stem cells, which can self-renew and generate gametes, are unique stem cells in that they are solely dedicated to transmit genetic information from generation to generation. The germ cells have a special place in the life cycle because they must be able to retain the ability to recreate the organism, a property known as developmental totipotency. Several lines of evidence have suggested the extensive proliferation activity and pluripotency of prenatal, neonatal and adult germline stem cells. We showed that adult male germline stem cells, spermatogonial stem cells, can be converted into embryonic stem cell-like cells, which can differentiate into the somatic stem cells of three germ layers. Different cell types such as vascular, heart, liver, pancreatic and blood cells could also be obtained from these stem cells. Understanding how spermatogonial stem cells can give rise to pluripotent stem cells and how somatic stem cells differentiate into germ cells could give significant insight into the regulation of developmental totipotency as well as having important implications for male fertility and regenerative medicine.

Fig. 1

The cycle of germ cell development. Following germ line specification, PGCs appear first in the extraembryonic mesoderm. PGCs migrate to the genital ridge and actively proliferate. The development of postmigratory germ cells is sex-specific. Female germ cells enter meiosis and undergo meiotic arrest until after birth. Male germ cells enter mitotic arrest and are reactivated to initiate spermatogenesis after birth. Male germ cells develop to spermatogonial stem cells (SSCs), which differentiate to sperm after a highly complicated differentiation process.

Fig. 2

The cycle of pluripotency. Germ cells are able to be reprogrammed to pluripotent stem cells in all stages of development. ES, embryonic stem cells; EpSC, epiblast stem cells; EG, embryonic germ cells; mGSCs, multipotent germline stem cells; maGSCs, multipotent germline stem cells.

Fig. 3

Perspective of the cell therapeutic approaches using spermatogonial stem cells. Spermatogonial stem cells are pluripotent stem cells and can be differentiated to different cell types, including sperm. Human SSCs can be used in cell-based regenerative medicine. SSCs can be used for therapy of genetically determined diseases, if homologous recombination in the cells works successfully. Finally, SSCs can recover fertility of cancer patients after chemotherapy and radiation treatment.