Persistent competition among stem cells and their daughters in the Drosophila ovary germline niche
Persistent competition among stem cells and their daughters in the Drosophila ovary germline niche
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DOI：
10.1242/dev.033340
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发表时间：
2009-03-15
期刊：
影响因子：
4.6
通讯作者：
Moreno, Eduardo
中科院分区：
文献类型：
--
作者：
Rhiner, Christa;Diaz, Begona;Moreno, Eduardo
细胞竞争是一种短距离的细胞-细胞相互作用，导致以失败者为代价的赢家细胞的增殖，尽管任一细胞类型在同型环境中显示正常生长。果蝇Myc（dMyc; DM-FlyBase）是翅上皮细胞竞争的有效诱导剂，但其在卵巢生殖系干细胞龛中的作用尚不清楚。在这里，我们表明，具有相对较低水平的dMyc的生殖系干细胞（GSC）被具有较高水平的dMyc的GSC所取代。相比之下，dMyc过表达的GSC在不影响总干细胞数量的情况下胜过野生型干细胞。我们还提供了由高dMyc表达干细胞和低dMyc表达后代形成的天然细胞竞争边界的证据，这可能有助于代谢活性高dMyc干细胞中利基提供的自我更新因子BMP/Dpp的浓度。在整个种系中施加统一的dMyc水平的遗传操作产生扩展的Dpp信号传导结构域并引起不协调的分化事件。我们提出，dMyc诱导的竞争在调节最佳干细胞库和尖锐的分化边界方面起着双重作用，但在新出现的dMyc复制的情况下可能是有害的，这些复制有利于癌前干细胞的生态位占据。此外，干细胞之间的竞争性相互作用可能与干细胞疗法在人类中的成功应用有关。
Cell competition is a short-range cell-cell interaction leading to the proliferation of winner cells at the expense of losers, although either cell type shows normal growth in homotypic environments. Drosophila Myc (dMyc; Dm-FlyBase) is a potent inducer of cell competition in wing epithelia, but its role in the ovary germline stem cell niche is unknown. Here, we show that germline stem cells (GSCs) with relative lower levels of dMyc are replaced by GSCs with higher levels of dMyc. By contrast, dMyc-overexpressing GSCs outcompete wild-type stem cells without affecting total stem cell numbers. We also provide evidence for a naturally occurring cell competition border formed by high dMyc-expressing stem cells and low dMyc-expressing progeny, which may facilitate the concentration of the niche-provided self-renewal factor BMP/Dpp in metabolically active high dMyc stem cells. Genetic manipulations that impose uniform dMyc levels across the germline produce an extended Dpp signaling domain and cause uncoordinated differentiation events. We propose that dMyc-induced competition plays a dual role in regulating optimal stem cell pools and sharp differentiation boundaries, but is potentially harmful in the case of emerging dmyc duplications that facilitate niche occupancy by pre-cancerous stem cells. Moreover, competitive interactions among stem cells may be relevant for the successful application of stem cell therapies in humans.