Stem cell niches are dynamic microenvironments that balance stem cell activity to maintain tissue homeostasis and repair throughout the lifetime of an organism. The development of strategies to monitor and perturb niche components has provided insight into the responsive nature of the niche and offers a framework to uncover how disruption of normal stem cell niche function may contribute to aging and disease onset and progression. Additional work in the identification of genetic factors that regulate the formation, activity, and size of stem cell niches will facilitate incorporation of the niche into stem cell-based therapies and regenerative medicine.

Adult stem cells reside in specialized microenvironments, or niches, that have an important role in regulating stem cell behaviour1. Therefore, tight control of niche number, size and function is necessary to ensure the proper balance between stem cells and progenitor cells available for tissue homeostasis and wound repair. The stem cell niche in the Drosophila male gonad is located at the tip of the testis where germline and somatic stem cells surround the apical hub, a cluster of approximately 10-15 somatic cells that is required for stem cell self-renewal and maintenance2-4. Here we show that somatic stem cells in the Drosophila testis contribute to both the apical hub and the somatic cyst cell lineage. The Drosophila orthologue of epithelial cadherin (DE-cadherin) is required for somatic stem cell maintenance and, consequently, the apical hub. Furthermore, our data indicate that the transcriptional repressor escargot regulates the ability of somatic cells to assume and/or maintain hub cell identity. These data highlight the dynamic relationship between stem cells and the niche and provide insight into genetic programmes that regulate niche size and function to support normal tissue homeostasis and organ regeneration throughout life.Many stem cell niches include support cells that influence stem cell behaviour through secretion of diffusible molecules. Physical contact between stem cells and support cells and/ or the extracellular matrix holds stem cells within the niche and close to self-renewal signals. Furthermore, niches provide spatial and mechanical cues that influence the fate of stem cell daughters. Therefore, the stem cell niche has an important role in regulating stem cell maintenance, self-renewal and survival (reviewed in ref. 5). However, little is known about the factors that regulate niche maintenance or size.Approximately ten somatic cells, called the hub, are found at the apical tip of the Drosophila testis (Fig. 1a)2. Germline stem cells (GSCs) and somatic stem cells (SSCs) surround and are in contact with hub cells. Whereas GSCs sustain spermatogenesis, SSCs produce cyst cells that encapsulate the maturing germ cells and ensure differentiation6,7. Hub cells secrete the growth factor Unpaired (Upd)3,4, which activates the JAK-STAT signal transduction pathway in adjacent stem cells. JAK-STAT signalling is necessary for stem cell maintenance and is sufficient to specify self-renewal of both GSCs and SSCs in the testis3,4,8.The apical hub is typically described as a post-mitotic, static structure. However, in agametic flies, SSCs proliferate and express hub markers, leading to an apparent expansion of the apical We proposed that SSCs may serve as a source of cells that contribute to the apical hub and, consequently, the stem cell niche. To address whether SSCs give rise to hub cells, positively marked β-galactosidase-expressing (β-gal + ) SSCs were generated using mitotic recombination, a technique typically used for lineage tracing analyses. Labelled SSCs were generated by heatshockin...

Summary Stem cells reside within specialized microenvironments, or niches, that control many aspects of stem cell behaviour. Somatic hub cells in the Drosophila testis regulate the behaviour of cyst stem cells (CySCs) and germline stem cells (GSCs) and are a primary component of the testis stem cell niche. The shutoff (shof) mutation, characterized by premature loss of GSCs and CySCs, was mapped to a locus encoding the evolutionarily conserved transcription factor Escargot (Esg). Hub cells depleted of Esg acquire CySC characteristics and differentiate as cyst cells, resulting in complete loss of hub cells and eventually, CySCs and GSCs, similar to the shof mutant phenotype. We identified Esg-interacting proteins and demonstrate an interaction between Esg and the co-repressor C-terminal binding protein (CtBP), which was also required for maintenance of hub cell fate. Our results indicate that niche cells can acquire stem cell properties upon removal of a single transcription factor in vivo.

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