Germ cells commit somatic stem cells to differentiation following priming by PI3K/Tor activity in the Drosophila testis.
Germ cells commit somatic stem cells to differentiation following priming by PI3K/Tor activity in the Drosophila testis.
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DOI：
10.1371/journal.pgen.1009609
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发表时间：
2021-12
期刊：
影响因子：
4.5
通讯作者：
Amoyel M
中科院分区：
文献类型：
--
作者：
Yuen AC;Hillion KH;Wang R;Amoyel M
干细胞子体分化的潜力如何以及何时变得有限，目前还知之甚少。虽然有人认为，来自利基的信号被积极地要求阻止分化，但另一个模型提出，干细胞可以在多个状态之间可逆地转移，其中一些状态已经准备好了，但没有承诺分化。在果蝇的睾丸中，体细胞囊泡干细胞(CySCs)产生囊泡细胞，囊泡细胞包裹生殖系以支持其发育。我们发现，如果PI3K/Tor途径的活性被抑制，CySCs的维持不依赖于生态位自我更新信号。相反，PI3K/Tor不足以单独驱动分化，这表明它为细胞分化提供了许可。事实上，我们发现，随着PI3K/Tor的升高，细胞周期干细胞的分化需要胚系，这表明对分化的最终承诺涉及几个步骤和细胞间的沟通。我们认为CySC子代细胞是可塑性的，它们的命运取决于邻近生殖细胞的可用性，PI3K/Tor作用于诱导CySC子代细胞处于启动状态，从而实现与生殖系的协调分化。干细胞的独特之处在于，它们能够通过分裂来再生成人组织，提供新的干细胞，这一过程被称为自我更新，以及分化和维持组织功能的细胞。分化的女儿是如何以及何时失去自我更新能力的，人们仍然知之甚少。自我更新依赖于干细胞所在的支持性微环境或利基环境提供的信号。有人认为，仅仅失去对这种环境及其提供的信号的接触就足以指导区分。在这里，我们使用果蝇的睾丸作为模型，以表明情况并非如此。相反，必须通过信号主动诱导分化，剥夺所有信号的干细胞才能得以维持。研究各种投入对分化的相对时间安排，使我们提出一系列事件确保适当的分化。首先，干细胞接收分化诱导信号，促进一种允许或启动的状态，这种状态是可逆的，不排除自我更新。最终的承诺来自于与组织中的其他细胞相互作用，确保构成该组织的不同细胞类型之间的分化总是以协调的方式发生。
How and when potential becomes restricted in differentiating stem cell daughters is poorly understood. While it is thought that signals from the niche are actively required to prevent differentiation, another model proposes that stem cells can reversibly transit between multiple states, some of which are primed, but not committed, to differentiate. In the Drosophila testis, somatic cyst stem cells (CySCs) generate cyst cells, which encapsulate the germline to support its development. We find that CySCs are maintained independently of niche self-renewal signals if activity of the PI3K/Tor pathway is inhibited. Conversely, PI3K/Tor is not sufficient alone to drive differentiation, suggesting that it acts to license cells for differentiation. Indeed, we find that the germline is required for differentiation of CySCs in response to PI3K/Tor elevation, indicating that final commitment to differentiation involves several steps and intercellular communication. We propose that CySC daughter cells are plastic, that their fate depends on the availability of neighbouring germ cells, and that PI3K/Tor acts to induce a primed state for CySC daughters to enable coordinated differentiation with the germline. Stem cells are unique in their ability to regenerate adult tissues by dividing to provide new stem cells, a process called self-renewal, and cells that will differentiate and maintain tissue function. How and when the daughters that differentiate lose the ability to self-renew is still poorly understood. Self-renewal depends on signals that are provided by the supportive micro-environment, or niche, in which the stem cells reside. It was assumed that simply losing access to this environment and the signals it provides was sufficient to direct differentiation. Here we use the Drosophila testis as a model to show that this is not the case. Instead, differentiation must be actively induced by signalling, and stem cells deprived of all signals can be maintained. Studying the relative timings of the various inputs into differentiation leads us to propose that a series of events ensure appropriate differentiation. First, stem cells receive differentiation-inducing signals that promote a permissive, or primed, state which is reversible and does not preclude self-renewal. The final commitment comes from interacting with other cells in the tissue, ensuring that differentiation always occurs in a coordinated manner among the different cell types composing this tissue.
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