Regulation of Self-renewal and Differentiation in Adult Stem Cell Lineages: Lessons from the Drosophila Male Germ Line

The ability to identify stem cells and trace their descendants in vivo has yielded insights into how self-renewal, proliferation, and differentiation are regulated in adult Stein Cell lineages. Analysis of male germ-line stein cells in Drosophila has revealed the importance of local signals from the microenvironment, the stein cell niche, in controlling stein cell behavior. Germ-line stein cells physically attach to the niche via localized adherens junctions that provide a polarity cue for orientation of centro-somes in interphase and the spindle in mitosis. As it result, stein cells divide asymmetrically: One daughter inherits attachment to the niche and remains within its embrace, whereas the other is displaced away and initiates differentiation. Strikingly, much as leukemia inhibitory factor (LIF) and transforming growth factor-beta (TGF-beta) signaling maintain mouse embryonic stein (ES) cells, maintenance of stem cell state in the Drosophila male germ line is regulated by cytokine-like signals from hub cells that activate the transcription factor STAT (signal transducer and activator of transcription) and TGF-beta class signals front Surrounding support cells that repress expression of a key differentiation factor. Surprisingly, transit-amplifying cells can revert to the stein cell state if they reoccupy the niche. Upon cessation of mitosis and the switch to terminal differentiation, genii cells express cell-type- and stage-specific transcription machinery components that drive expression of terminal differentiation genes, in part by removing Polycomb transcriptional silencing machinery.