Leatherman Judith L, Dinardo Stephen
Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Cell Stem Cell. 2008 Jul 3;3(1):44-54. doi: 10.1016/j.stem.2008.05.001.
The ability of adult stem cells to maintain their undifferentiated state depends upon residence in their niche. While simple models of a single self-renewal signal are attractive, niche-stem cell interactions are likely to be more complex. Many niches have multiple cell types, and the Drosophila testis is one such complex niche with two stem cell types, germline stem cells (GSCs) and somatic cyst progenitor cells (CPCs). These stem cells require chemokine activation of Jak/STAT signaling for self-renewal. We identified the transcriptional repressor Zfh-1 as a presumptive somatic target of Jak/STAT signaling, demonstrating that it is necessary and sufficient to maintain CPCs. Surprisingly, sustained zfh-1 expression or intrinsic STAT activation in somatic cells caused neighboring germ cells to self-renew outside their niche. In contrast, germline-intrinsic STAT activation was insufficient for GSC renewal. These data reveal unexpected complexity in cell interactions in the niche, implicating CPCs in GSC self-renewal.
成体干细胞维持其未分化状态的能力取决于其在特定微环境中的驻留。虽然单一自我更新信号的简单模型很有吸引力,但微环境与干细胞之间的相互作用可能更为复杂。许多微环境包含多种细胞类型,果蝇睾丸就是这样一个复杂的微环境,其中有两种干细胞类型,即生殖系干细胞(GSCs)和体细胞囊肿祖细胞(CPCs)。这些干细胞需要趋化因子激活Jak/STAT信号通路来进行自我更新。我们鉴定出转录抑制因子Zfh-1是Jak/STAT信号通路的一个假定体细胞靶点,证明它对于维持CPCs是必要且充分的。令人惊讶的是,体细胞中持续的zfh-1表达或内在的STAT激活会导致邻近的生殖细胞在其微环境之外进行自我更新。相反,生殖系内在的STAT激活不足以实现GSC更新。这些数据揭示了微环境中细胞相互作用出人意料的复杂性,表明CPCs参与了GSC自我更新。