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TORC1 is required to balance cell proliferation and cell death in planarians

机译:需要TORC1来平衡涡虫中的细胞增殖和细胞死亡

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摘要

Multicellular organisms are equipped with cellular mechanisms that enable them to replace differentiated cells lost to normal physiological turnover, injury, and for some such as planarians, even amputation. This process of tissue homeostasis is generally mediated by adult stem cells (ASCs), tissue-specific stem cells responsible for maintaining anatomical form and function. To do so, ASCs must modulate the balance between cell proliferation, i.e. in response to nutrients, and that of cell death, i.e. in response to starvation or injury. But how these two antagonistic processes are coordinated remains unclear. Here, we explore the role of the core components of the TOR pathway during planarian tissue homeostasis and regeneration and identified an essential function for TORC1 in these two processes. RNAi-mediated silencing of . TOR in intact animals resulted in a significant increase in cell death, whereas stem cell proliferation and stem cell maintenance were unaffected. Amputated animals failed to increase stem cell proliferation after wounding and displayed defects in tissue remodeling. Together, our findings suggest two distinct roles for TORC1 in planarians. TORC1 is required to modulate the balance between cell proliferation and cell death during normal cell turnover and in response to nutrients. In addition, it is required to initiate appropriate stem cell proliferation during regeneration and for proper tissue remodeling to occur to maintain scale and proportion.
机译:多细胞生物体具备细胞机制,使它们能够替代因正常生理更新,损伤以及某些人(例如,涡虫,甚至是截肢)而丢失的分化细胞。组织动态平衡的过程通常由成体干细胞(ASC)介导,成体干细胞是负责维持解剖形态和功能的组织特异性干细胞。为此,ASC必须调节细胞增殖(即响应营养)和细胞死亡(即响应饥饿或伤害)之间的平衡。但是,如何协调这两个对抗过程仍不清楚。在这里,我们探讨了涡流通路核心元件在平面组织稳态和再生过程中的作用,并确定了这两个过程中TORC1的基本功能。 RNAi介导的沉默。完整动物中的TOR导致细胞死亡显着增加,而干细胞增殖和干细胞维持不受影响。截肢动物受伤后未能增加干细胞增殖,并在组织重塑中表现出缺陷。在一起,我们的发现表明TORC1在平面学家中有两个不同的角色。在正常细胞更新过程中以及对营养物质的响应中,需要TORC1调节细胞增殖与细胞死亡之间的平衡。另外,需要在再生过程中启动适当的干细胞增殖,并进行适当的组织重塑以维持规模和比例。

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