Mouse Cancer Genetics Program, National Institutes of Health, National Cancer Institute at Frederick, Frederick, Maryland 21702, USA.
J Cell Physiol. 2010 May;223(2):500-10. doi: 10.1002/jcp.22073.
In many tissues, two or more types of stem cells share a niche, and how the stem cells coordinate their self-renewal and differentiation is poorly understood. In the Drosophila testis, germ line stem cells (GSCs) and somatic cyst progenitor cells (CPCs) contact each other and share a niche (the hub). The hub expresses a growth factor unpaired (Upd) that activates the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway in GSCs to regulate the stem cell self-renewal. Here, we demonstrate that the JAK/STAT signaling also regulates CPCs self-renewal. We also show that a negative regulator, the suppressor of cytokine signaling 36E (SOCS36E), suppresses JAK/STAT signaling in somatic cells, preventing them from out-competing the GSCs. Furthermore, through selectively manipulating the JAK/STAT signaling level in either CPCs or GSCs, we demonstrate that the somatic JAK/STAT signaling is essential for self-renewal and maintenance of both CPCs and GSCs. These data suggest that a single JAK/STAT signal from the niche orchestrate the competitive and dependent co-existence of GSCs and CPCs in the Drosophila testis niche.
在许多组织中,两种或更多类型的干细胞共享一个龛位,而干细胞如何协调自我更新和分化还知之甚少。在果蝇的睾丸中,生殖系干细胞(GSCs)和体腔祖细胞(CPCs)相互接触并共享一个龛位(中心)。该中心表达一种未配对的生长因子(Upd),该因子在 GSCs 中激活 Janus 激酶/信号转导和转录激活因子(JAK/STAT)途径,以调节干细胞的自我更新。在这里,我们证明 JAK/STAT 信号也调节 CPCs 的自我更新。我们还表明,一种负调控因子,细胞因子信号转导抑制因子 36E(SOCS36E),抑制体细胞中的 JAK/STAT 信号,防止它们与 GSCs 竞争。此外,通过选择性地在 CPCs 或 GSCs 中操纵 JAK/STAT 信号水平,我们证明了体细胞 JAK/STAT 信号对于 CPCs 和 GSCs 的自我更新和维持都是必不可少的。这些数据表明,龛位中来自单一 JAK/STAT 信号协调了果蝇睾丸龛位中 GSCs 和 CPCs 的竞争和依赖共存。