Stem cells reside in niches that provide signals to maintain self-renewal, and differentiation is viewed as a passive process that depends on loss of access to these signals. Here, we demonstrate that the differentiation of somatic cyst stem cells (CySCs) in the Drosophila testis is actively promoted by PI3K/Tor signaling, as CySCs lacking PI3K/Tor activity cannot differentiate properly. We find that an insulin peptide produced by somatic cells immediately outside of the stem cell niche acts locally to promote somatic differentiation through Insulin-like receptor (InR) activation. These results indicate that there is a local ‘differentiation' niche that upregulates PI3K/Tor signaling in the early daughters of CySCs. Finally, we demonstrate that CySCs secrete the Dilp-binding protein ImpL2, the Drosophila homolog of IGFBP7, into the stem cell niche, which blocks InR activation in CySCs. Thus, we show that somatic cell differentiation is controlled by PI3K/Tor signaling downstream of InR and that the local production of positive and negative InR signals regulates the differentiation niche. These results support a model in which leaving the stem cell niche and initiating differentiation are actively induced by signaling.
Author contributions
M.A. designed the experiments with contributions from E.A.B.; M.A., K.-H.H., S.R.M. and E.A.B. performed the experiments and analyzed the data; M.A. and E.A.B. wrote the manuscript.
Funding
This work was supported by the National Institutes of Health [R01 GM085075 to E.A.B.]; and the New York State Department of Health NYSTEM [C028132 to E.A.B.]. M.A. was funded by a Helen L. and Martin S. Kimmel Center for Stem Cell Biology Senior Postdoc Fellowship. Deposited in PMC for release after 12 months.
