Tissue regeneration and homeostasis often require recruitment of undifferentiated precursors (adult stem cells; ASCs). While many ASCs continuously proliferate throughout the lifetime of an organism, others are recruited from a quiescent state to replenish their target tissue. A long-standing question in stem cell biology concerns how long-lived, non-dividing ASCs regulate the transition between quiescence and proliferation. We study the melanocyte stem cell (MSC) to investigate the molecular pathways that regulate ASC quiescence. Our prior work indicated that GABA-A receptor activation promotes MSC quiescence in larval zebrafish. Here, through pharmacological and genetic approaches we show that GABA-A acts through calcium signaling to maintain MSC quiescence. Unexpectedly, we identified translocator protein (TSPO), a mitochondrial membrane-associated protein that regulates mitochondrial function and metabolic homeostasis, as a parallel regulator of MSC quiescence. We found that both TSPO-specific ligands and induction of gluconeogenesis likely act in the same pathway to promote MSC activation and melanocyte production in larval zebrafish. In contrast, TSPO and gluconeogenesis appear to act in parallel to GABA-A receptor signaling to regulate MSC quiescence and vertebrate pigment patterning.

中文翻译：

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GABA-A 受体和线粒体 TSPO 信号传导并行作用，调节斑马鱼幼虫黑素细胞干细胞的静止状态。

组织再生和体内平衡通常需要招募未分化的前体细胞（成体干细胞；ASC）。虽然许多 ASC 在生物体的整个生命周期中不断增殖，但其他 ASC 是从静止状态招募来补充其目标组织的。干细胞生物学中一个长期存在的问题是长寿、不分裂的 ASC 如何调节静止和增殖之间的过渡。我们研究黑素细胞干细胞 (MSC)，以研究调节 ASC 静止的分子途径。我们之前的工作表明，GABA-A 受体激活可促进斑马鱼幼虫的 MSC 静止。在这里，通过药理学和遗传学方法，我们证明 GABA-A 通过钙信号传导维持 MSC 静止。出乎意料的是，我们发现易位蛋白（TSPO）是一种调节线粒体功能和代谢稳态的线粒体膜相关蛋白，作为 MSC 静止的平行调节因子。我们发现 TSPO 特异性配体和糖异生诱导可能在同一途径中发挥作用，促进斑马鱼幼虫中 MSC 的活化和黑素细胞的产生。相比之下，TSPO 和糖异生似乎与 GABA-A 受体信号传导并行作用，调节 MSC 静止和脊椎动物色素图案。