Wnt signaling-mediated redox regulation maintains the germ line stem cell differentiation niche.
Wnt signaling-mediated redox regulation maintains the germ line stem cell differentiation niche.
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作者：
Wang S;Gao Y;Song X;Ma X;Zhu X;Mao Y;Yang Z;Ni J;Li H;Malanowski KE;Anoja P;Park J;Haug J;Xie T
成体干细胞不断进行自我更新并产生分化的细胞。在果蝇卵巢中，两个独立的小生境控制生殖系干细胞（GSC）的自我更新和分化过程。与自我更新生态位相比，分化生态位的维持和功能知之甚少。在这项研究中，我们表明，Wnt信号调节的细胞氧化还原状态是至关重要的维持和功能的分化生态位，以促进GSC后代分化。缺陷的Wnt信号传导导致分化的GSC后代中分化生态位的丧失和BMP信号传导的上调，从而破坏生殖细胞分化。从机制上讲，Wnt信号传导控制多个谷胱甘肽-S-转移酶家族基因的表达和细胞氧化还原状态。最后，Wnt 2和Wnt 4冗余地起作用以维持分化小生境中的活性Wnt信号传导。因此，本研究揭示了Wnt信号在调节细胞氧化还原状态和维持分化生态位中的新策略。DOI：http://dx.doi.org/10.7554/eLife.08174.001动物或植物有许多不同类型的细胞，在生物体的生命中有特定的作用。这些细胞组成组织。在成年动物的大多数组织中，称为干细胞的小细胞群负责替换由于疾病，损伤或作为正常身体维护的一部分而丢失的其他细胞。雌性果蝇的“生殖系”干细胞（产生雌性性细胞（或卵子））是研究干细胞如何调节的有效系统。这些细胞生活在卵巢的一个称为干细胞龛的区域。每次干细胞分裂，它产生一个干细胞和另一个子细胞。然后，这个子细胞进入另一个称为“分化”的小生境，并经历一系列分裂，产生卵细胞。分化小生境是由护送细胞形成的，对产生卵细胞至关重要，但目前尚不清楚护送细胞如何促进这一过程，或如何维持小生境。Wang等人现在已经更详细地研究了分化生态位。实验表明，一种称为Wnt信号传导的细胞通讯系统通过控制护送细胞生长和分裂的能力来维持分化生态位。如果Wnt信号传导有缺陷，分化生态位就会丢失，从而破坏卵细胞的形成。进一步的实验表明，在分化小生境中的两种称为Wnt 2和Wnt 4的蛋白质-它们激活Wnt信号-作为信号调节小生境，主要通过控制四个特定基因的表达。这四个基因编码的酶可以清除细胞中的“活性氧”。Wang等人的发现揭示了Wnt信号在维持分化生态位中的重要作用。下一步是弄清楚这是如何工作的细节。DOI：http://dx.doi.org/10.7554/eLife.08174.002网站
Adult stem cells continuously undergo self-renewal and generate differentiated cells. In the Drosophila ovary, two separate niches control germ line stem cell (GSC) self-renewal and differentiation processes. Compared to the self-renewing niche, relatively little is known about the maintenance and function of the differentiation niche. In this study, we show that the cellular redox state regulated by Wnt signaling is critical for the maintenance and function of the differentiation niche to promote GSC progeny differentiation. Defective Wnt signaling causes the loss of the differentiation niche and the upregulated BMP signaling in differentiated GSC progeny, thereby disrupting germ cell differentiation. Mechanistically, Wnt signaling controls the expression of multiple glutathione-S-transferase family genes and the cellular redox state. Finally, Wnt2 and Wnt4 function redundantly to maintain active Wnt signaling in the differentiation niche. Therefore, this study has revealed a novel strategy for Wnt signaling in regulating the cellular redox state and maintaining the differentiation niche. DOI: http://dx.doi.org/10.7554/eLife.08174.001 An animal or plant has many different types of cells that have specific roles in the life of the organism. These cells are organized into tissues. In most tissues in adult animals, small groups of cells called stem cells are responsible for replacing the other cells that have been lost due to disease, injury, or as part of normal body maintenance. The ‘germ line’ stem cells of female fruit flies—which produce female sex cells (or eggs)—are an effective system for studying how stem cells are regulated. These cells live in an area of the ovary called a stem cell niche. Each time a stem cell divides, it produces one stem cell and one other daughter cell. This daughter cell then moves into another niche called the ‘differentiation’ niche and undergoes a series of divisions that produce the egg cells. The differentiation niche is formed by escort cells and is crucial for producing the egg cells, but it is not clear how the escort cells promote this process, or how the niche is maintained. Wang et al. have now studied the differentiation niche in more detail. The experiments show that a cell communication system called Wnt signaling maintains the differentiation niche by controlling the ability of the escort cells to grow and divide. If Wnt signaling is defective, the differentiation niche is lost, which disrupts the formation of egg cells. Further experiments show that two proteins called Wnt2 and Wnt4 in the differentiation niche—which activate Wnt signaling—act as signals to regulate the niche, mainly by controlling the expression of four particular genes. These four genes encode enzymes that remove ‘reactive oxygen species’ from cells. Wang et al.'s findings have revealed an important role for Wnt signaling in maintaining the differentiation niche. The next step is to figure out the details of how this works. DOI: http://dx.doi.org/10.7554/eLife.08174.002