The molecular mechanisms that underlie stem-cell maintenance and differentiation are poorly understood. Brawley and Matunis now show, in a report in Science, that male germline stem cells (GSCs) in the Drosophila melanogaster testis can be replaced by dedifferentiated spermatogonia, which then repopulate the stem-cell microenvironment (or 'stem-cell niche').

Stem cells in the D. melanogaster male germline are maintained by local activation of the JAK (Janus kinase)–STAT (signal transducer and activator of transcription) pathway. In the absence of JAK–STAT signalling, GSCs differentiate into spermatogonia and spermatocytes without self-renewal. Indeed, this is what happened when the authors used a temperature-sensitive allele of the D. melanogaster STAT homologue stat92E (stat92EF) under nonpermissive conditions.

But, what happens when stat92E function is restored by shifting the temperature to permissive conditions? Cells that were negative for a spermatogonial differentiation marker returned to the hub (a cluster of somatic cells that forms the stem-cell niche) in most testes. And, the number of testes that contained GSCs increased from 22.5% to 75.8%. This implies that testes that completely lacked GSCs regained them by some kind of dedifferentiation process.

Male flies that had been allowed to differentiate at the nonpermissive temperature until they no longer contained spermatogonia, but only spermatocytes, never regained GSCs after signalling was restored. This indicates that it is spermatogonia, but not spermatocytes, that dedifferentiate to replace the GSCs.

Spermatogonia exist as multicellular cysts, which must somehow break away to become GSCs when JAK–STAT signalling is restored. Brawley and Matunis showed this by labelling spermatogonia with bromodeoxyuridine before reactivating the signalling pathway. Labelled cysts were detected near the hub in 6% of testes before recovery. And after signalling was reactivated, again, 6% of testes contained labelled GSCs. This suggests that GSCs must be breakdown products of labelled cysts.

The authors concluded that the partially differentiated spermatogonia must have remarkable plasticity by dedifferentiating into stem cells in response to signals from the stem-cell niche. This dedifferentiation mechanism contributes to stem-cell maintenance and renewal.