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No consistent spindle orientation was observed

No consistent spindle orientation was observed. (d) PF-06651600 Mouse spermatogonia stem cell (SSC) niche. be relatively dispensable (in that they will be worn out soon or later anyways), neither of GSC daughters is usually dispensable. GSCs must be guarded to prevent tumorigenesis and tissue degeneration, while differentiating cells must be guarded to accurately transmit genetic information to the next generation. The mechanisms by which GSCs fulfill these possibly contradictory requirements are not comprehended. Recent research has revealed many features of GSCs to be consistent PF-06651600 with their identity as stem cells. These characteristics include mechanisms of stem cell self-renewal, asymmetric division as a means of tissue homeostasis, and influence of the stem cell niche. These findings show that many aspects of stem cell biology are conserved in GSCs. These results, combined with the simple characteristics of GSCs, including unipotency and a high proliferation rate, have advanced the study of adult stem cell biology. Daughters of GSCs must decide whether to either retain the same characteristics as stem cells (self-renewal) or to initiate differentiation. The determination of cell fate is critical for long-term tissue homeostasis, maintaining the pipeline of gamete production while preserving the stem cell populace. During steady-state tissue homeostasis, asymmetric stem cell division can contribute to this balance. Also, as is the case for many other stem cells, GSCs are often found in the stem cell niche, a microenvironment that specifies stem cell identity. Here we summarize recent findings on these topics regarding GSCs, mainly from Drosophila, C. elegans, and mouse, in the framework of important concepts in the adult stem cell biology. Signaling pathway for maintaining stemness; self-renewal The term CACNA1D stem cell self-renewal refers to the phenomenon that upon division, stem cells produce stem cells with their initial characteristics. Unlike many other adult stem cells, GSCs are unipotent, producing only either sperm or eggs. Although there are striking similarities in GSCs among different species, the signaling pathways that govern their stemness appear to be divergent. In Drosophila, GSCs typically divide asymmetrically to produce one stem cell and one differentiating cell. The PF-06651600 differentiating cell then undergoes exactly four transit-amplifying divisions, yielding 16 interconnected germ cells, before entering meiosis (Physique 1). In Drosophila male GSCs, the JAK (Janus kinase)-STAT (Signal transducer and activator of transcription) pathway is essential for self-renewal of GSCs[1](Physique 1a). Loss-of-function mutations of components of this pathway lead to rapid loss of GSCs in a cell-autonomous manner. However, the activation of the JAK-STAT pathway in GSCs is not sufficient for self-renewal. GSCs require inputs from surrounding cyst stem cells (CySCs) for stem cell identity [2]. Open in a separate window Physique 1 Anatomy of GSC niches(a) Drosophila male GSC niche. GSCs and cyst stem cells (CySCs) are attached to hub cells via adherens junctions (purple crescents). GSCs divide asymmetrically to self-renew and produce a differentiating gonialblast (GB). The GB undergoes four synchronous, transit-amplifying divisions to yield 16 interconnected spermatogonia, through which the fusome (red lines) run. The spectrosome (red sphere) is the spherical version of the fusome found in GSCs. A pair of CySCs encapsulates the GSCs and provides the signals required for GSC identity. Similar to GSCs, CySCs are thought to divide asymmetrically to self-renew and produce cyst cells. Cyst cells exit the cell cycle, a pair of which encapsulates the GB and spermatogonia to promote differentiation. Hub cells secrete the Unpaired (Upd) ligand to activate the JAK-STAT signaling PF-06651600 PF-06651600 pathway in both GSCs and CySCs to specify their stem cell identity. The Zfh-1 transcription factor acts downstream of the JAK-STAT to specify CySC identity. EGFR signaling ensures the encapsulation of germ cells by cyst cells. The mitotic spindle in GSCs is usually oriented to ensure the asymmetric stem cell division by positioning a mother centrosome (yellow star) toward the hub and GSC interface. GB and spermatogonia can dedifferentiate to regain GSC.