Germ cell tumours reveal a population of pluripotent adult stem cells in the testis

The unique ability of pluripotent stem cells to self-renew without differentiating is precisely regulated by a relatively small network of transcription factors, including the Nanog gene, discovered in the Hart laboratory (Hart et al., 2004). During normal development, the Nanog gene is expressed only in pluripotent stem cells, including embryonic stem cells, the inner cell mass and primordial germ cells. We discovered that re-expression of this pluripotency gene is a diagnostic marker for human germ cell tumours, including carcinoma in-situ and embryonal carcinoma (Hart et al., 2005).

These discoveries have led us to investigate the role of Nanog in germline development and tumorigenesis in greater detail. We have now modified the mouse Nanog gene, introducing the bacterial beta-galactosidase (LacZ) reporter gene, allowing for the first time a sensitive and accurate assessment of Nanog gene expression during normal development and in cell culture. We find that Nanog is expressed at low levels in the stem cell compartment of normal adult testis. Thus, Nanog expression may mark a novel pluripotent stem cell population in the testis.

This discovery has important implications for germ cell cancer and also for regenerative medicine. If pluripotent stem cells could be isolated from the adult testis, they could potentially be utilised in cell based medicine for neurodegenerative disease, diabetes or repairing damaged cardiac or renal tissue following heart attack or kidney failure.