Editors' ChoiceDevelopment

Stemming Displacement

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Sci. Signal.  06 Oct 2009:
Vol. 2, Issue 91, pp. ec328
DOI: 10.1126/scisignal.291ec328

Stem cell niches regulate the self-renewal, specification, and differentiation of stem cells. In the testis of the fruit fly Drosophila melanogaster, two populations of stem cells (germline stem cells, or GSCs, and somatic cyst progenitor cells, or CPCs) are maintained by direct contact with the hub, a cluster of somatic cells that acts as the stem cell niche. GSC and CPC self-renewal depends on signaling through the Janus kinase–signal transducer and activator of transcription (JAK-STAT) pathway in response to hub production of the JAK-STAT ligand Unpaired (Upd). As GSC and CPC daughter cells are displaced from the hub, they differentiate to form spermatogonia. Issigonis et al. report that the suppressor of cytokine signaling 36E (SOCS36E), an inhibitor of the JAK-STAT pathway that is itself transcriptionally activated by JAK-STAT signaling, is specifically required in CPCs to prevent them from displacing GSCs at the hub. In wild-type testes, a large portion of each GSC cell contacts the hub, whereas only a small portion of each CPC contacts the hub. In testes from socs36e mutants, the number of GSCs was reduced relative to wild type, and the number of CPCs was unchanged, but a larger portion of each CPC contacted the hub. The abundance of βPS-integrin at sites of CPC-hub contact increased in socs36e mutants, and organism-wide inactivation of one copy of the gene encoding talin, a cytoskeletal protein required for integrin-mediated adhesion, prevented CPCs from displacing GSCs at the hub in the mutants. Thus, negative feedback of JAK-STAT signaling affects the balance between GSCs and CPCs at the hub by regulating competition between the two stem cell populations, perhaps by modulating integrin-mediated adhesion. In a related study, Sheng et al. report that JAK-STAT signaling not only is important for the maintenance of stem cells in the fly testis but also is required to establish the stem cell population—and that this population of stem cells is established in the embryo soon after hub formation.

M. Issigonis, N. Tulina, M. de Cuevas, C. Brawley, L. Sandler, E. Matunis, JAK-STAT signal inhibition regulates competition in the Drosophila testis stem cell niche. Science 326, 153–156 (2009). [Abstract] [Full Text]

X. R. Sheng, T. Posenau, J. J. Gumulak-Smith, E. Matunis, M. Van Doren, M. Wawersik, Jak-STAT regulation of male germline stem cell establishment during Drosophila embryogenesis. Dev. Biol. 334, 335–344 (2009). [PubMed]

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