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Germline self-renewal requires cyst stem cells and stat regulates niche adhesion in Drosophila testes

Abstract

Adults maintain tissue-specific stem cells through niche signals. A model for niche function is the Drosophila melanogaster testis, where a small cluster of cells called the hub produce locally available signals that allow only adjacent cells to self-renew. We show here that the principal signalling pathway implicated in this niche, chemokine activation of STAT1,2, does not primarily regulate self-renewal of germline stem cells (GSCs), but rather governs GSC adhesion to hub cells. In fact, GSC renewal does not require hub cell contact, as GSCs can be renewed solely by contact with the second resident stem cell population, somatic cyst stem cells (CySCs), and this involves BMP signalling. These data suggest a modified paradigm whereby the hub cells function as architects of the stem cell environment, drawing into proximity cellular components necessary for niche function. Self-renewal functions are shared by the hub cells and the CySCs. This work also reconciles key differences in GSC renewal between Drosophila testis and ovary niches, and highlights how a niche can coordinate the production of distinct lineages by having one stem cell type rely on a second.

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Figure 1: Germline stat depletion does not compromise self-renewal.
Figure 2: stat-depleted GSCs become displaced from the hub.
Figure 3: GSCs show hub adhesion defects before other signs of differentiation after global stat depletion.
Figure 4: Rescued GSCs are activated for and require the BMP pathway.

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Acknowledgements

We thank members of the fly community, Bloomington Stock Center, Vienna Drosophila Resource Center, and the Developmental Studies Hybridoma Bank for reagents. We thank Erika Matunis for helpful comments on the manuscript, and Seth Donoughe for technical assistance. This work was supported by NIH R01GM8060804 and 060804-10S1 to S.D.

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Experiments were conceived and analysed by J.L.L. and S.D; J.L.L. performed the experiments and wrote the manuscript; S.D. edited the manuscript.

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Correspondence to Stephen DiNardo.

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The authors declare no competing financial interests.

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Leatherman, J., DiNardo, S. Germline self-renewal requires cyst stem cells and stat regulates niche adhesion in Drosophila testes. Nat Cell Biol 12, 806–811 (2010). https://doi.org/10.1038/ncb2086

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