We all know that stem cells can generate any of the body's tissue types, but how do they renew themselves to prevent their own demise? Now, two reports in Science reveal some of the biological instructions for self-renewal. They have found that cells in the Drosophila testes act as a microenvironment and activate the JAK–STAT (Janus kinase–signal transducer and activator of transcription) signalling pathway, which determines the fate of stem cells by inhibiting their mortality and maturation.

In male Drosophila, the sperm stem cells lie at the tip of the testis, surrounding a cluster of cells called a hub. When the stem cell divides, the daughter cell maintaining contact with the hub remains a stem cell, whereas the cell that is displaced away becomes a blast cell and begins to develop into a male germ cell. What governs the destiny of each cell was unclear.

Kiger and colleagues, and Tulina and Matunis investigated whether cues from within the hub were an important factor. Both groups focused on the JAK–STAT pathway as JAK activation of STATs is known to activate target genes in both Drosophila and mammals. They created mutants for the JAK homologue hopscotch (Hop) or the STAT homologue Stat92E in stem cells, and found that if mutants lacked an active JAK–STAT pathway, the stem cells differentiated but did not self-renew. By contrast, ectopic or constitutive JAK–STAT signalling greatly expanded stem-cell numbers.

But how is the JAK–STAT pathway activated in these cells? Both groups found that cells in the hub act as a microenvironment by expressing a localized source of a signalling molecule called Unpaired, which activates the JAK–STAT pathway in adjacent stem cells. Although both groups did not inactivate Unpaired, they showed that misexpression was sufficient to cause expansion of the germ-line stem-cell population.

So, it seems that signals within the hub create a stem-cell microenvironment and that any daughter cells that are displaced will embark on a journey of differentiation into mature germ cells. Signals from surrounding cells that promote differentiation of displaced cells could help prevent excessive stem-cell proliferation, whereas hubs that lack stem cells could instruct both daughters of a neighbouring stem cell to self-renew and repopulate the microenvironment. Although this model will need to be further defined, it offers an intriguing insight into how stem-cell renewal can be achieved and regulated.