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

摘要

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 stem cell lineages. Analysis of male germ-line stem cells in Drosophila has revealedthe importance of local signals from the microenvironment, the stem cell niche, in controlling stem cell behavior. Germ-linestem 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 a result, stem cells divide asymmetrically: One daughter inherits attach-ment 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-I3 (TGF-(3) signaling maintain mouse embryonicstem (ES) cells, maintenance of stem cell state in the Drosophila male germ line is regulated by cytokine-like signals fromhub cells that activate the transcription factor STAT (signal transducer and activator of transcription) and TGF-l3 class signalsfrom surrounding support cells that repress expression of a key differentiation factor. Surprisingly, transit-amplifying cellscan revert to the stem cell state if they reoccupy the niche. Upon cessation of mitosis and the switch to terminal differentia-tion, germ cells express cell-type- and stage-specific transcription machinery components that drive expression of terminaldifferentiation genes, in part by removing Polycomb transcriptional silencing machinery.