Soluble factors mediate competitive and cooperative interactions between cells expressing different levels of Drosophila Myc
Soluble factors mediate competitive and cooperative interactions between cells expressing different levels of Drosophila Myc
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DOI：
10.1073/pnas.0709021104
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发表时间：
2007-11-20
影响因子：
11.1
通讯作者：
Johnston, Laura A.
中科院分区：
文献类型：
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作者：
Senoo-Matsuda, Nanami;Johnston, Laura A.
当发育中的果蝇翅膀中的相邻细胞表达不同水平的转录因子dMyc时，可能会发生竞争性相互作用。具有更多dMyc的细胞增殖并最终过度填充翼，而具有较少dMyc的细胞死亡，从而防止翼过度生长。细胞如何感知它们之间的dMyc活性差异以及导致竞争期间生长和存活变化的过程的性质仍然未知。我们已经开发了一种基于细胞培养的方法，通过使用果蝇S2细胞来研究细胞竞争的机制。我们发现，在体外共培养的S2细胞，表达不同水平的dMyc导致细胞的相互作用，概括了许多方面的细胞竞争中发展的翅膀。我们的数据表明，这两个细胞群体在共培养物中参与，并需要通过释放可溶性因子到培养基中的竞争过程。我们证明了幼稚细胞对竞争性共培养条件培养基的反应取决于其表达dMyc的潜力：能够表达高水平dMyc的细胞获得生存优势并增殖更快，而具有较低dMyc水平的细胞则被指示死亡。我们认为，细胞感知和响应局部Myc活性差异的能力是一种合作机制，可能有助于器官和组织在正常发育和再生过程中的生长调节和发育可塑性。
When neighboring cells in the developing Drosophila wing express different levels of the transcription factor, dMyc, competitive interactions can occur. Cells with more dMyc proliferate and ultimately overpopulate the wing, whereas cells with less dMyc die, thereby preventing wing overgrowth. How cells sense dMyc activity differences between themselves and the nature of the process leading to changes in growth and survival during competition remain unknown. We have developed a cell culture-based assay by using Drosophila S2 cells to investigate the mechanism of cell competition. We find that in vitro coculture of S2 cells that express different levels of dMyc leads to cellular interactions that recapitulate many aspects of cell competition in the developing wing. Our data indicate that both cell populations in the cocultures participate in and are required for the competitive process by releasing soluble factors into the medium. We demonstrate that the response of naive cells to medium conditioned with competitive cocultures depends on their potential to express dMyc: Cells that can express high levels of dMyc gain a survival advantage and proliferate faster, whereas cells with lower dMyc levels are instructed to die. We suggest that the ability of cells to perceive and respond to local differences in Myc activity is a cooperative mechanism that could contribute to growth regulation and developmental plasticity in organs and tissues during normal development and regeneration.