Stem cells in various somatic tissues (bone marrow, skeletal muscle) can be identified by the `Side Population' marker based on Hoechst 33342 efflux. We show that mouse testicular cells also display a `Side Population' that express Bcrp1 mRNA, the ABC transporter responsible for Hoechst efflux in hematopoietic cells. Inhibition of Hoechst efflux by specific BCRP1 inhibitor Ko143 show that germinal `Side Population' phenotype is dependent on BCRP1 activity. Analysis of two well-defined models of altered spermatogenesis(W/Wv mutants and cryptorchid male mice) and RNA expression studies of differentiation markers demonstrate that germinal `Side Population' contains spermatogonial cells. In addition,α 6-integrin and Stra8 germinal stem cell markers, are expressed in the `Side Population'. In vivo repopulation assay clearly establishes that testis `Side Population' in adult mice is highly enriched in male germ stem cells.

In adults, stem cells are responsible for the maintenance of many actively renewing tissues, such as haematopoietic, skin, gut and germinal tissues. These stem cells can self-renew or be committed to becoming progenitors. Stem-cell commitment is thought to be irreversible but in male and female Drosophila melanogaster, it was shown recently that differentiating germ cells can revert to functional stem cells that can restore germinal lineage. Whether progenitors are also able to generate stem cells in mammals remains unknown. Here we show that purified mouse spermatogonial progenitors committed to differentiation can generate functional germinal stem cells that can repopulate germ-cell-depleted testes when transplanted into adult mice. We found that GDNF, a key regulator of the stem-cell niche, and FGF2 are able to reprogram in vitro spermatogonial progenitors for reverse differentiation. This study supports the emerging concept that the stem-cell identity is not restricted in adults to a definite pool of cells that self-renew, but that stemness could be acquired by differentiating progenitors after tissue injury and throughout life.

Sera of 807 people living in a rural forest area in southern Cameroon were tested by enzyme-linked immunosorbent assay; 101 (12.5%) gave positive results and were confirmed by line immunoassay. There was a highly significant difference between subjects aged over 40 years and those under 40 years, with the former having a much higher prevalence of antibodies. There were also significant differences between antibody prevalences among subjects aged > 40 years in the 3 ethnic groups studied--Baka Pygmies (6%), Fangs (30%) and Boulous (44%). Further studies are necessary to determine the reasons for these differences.

No abstract