A feedforward loop between JAK/STAT downstream target p115 and STAT in germline stem cells

The maintenance of germline stem cells (GSCs) is essential for tissue homeostasis. JAK/STAT signaling maintains GSC fate in Drosophila testis. However, how JAK/STAT signaling maintains male GSC fate through its downstream targets remains poorly understood. Here, we identify p115, a tER/cis-Golgi golgin protein, as a putative downstream target of JAK/STAT signaling. p115 maintains GSC fate independent of GM130 and GRASP65. p115 localizes in cytosol, the ER and Golgi apparatus in germline cells and is required for the morphology of the ER and Golgi apparatus. Furthermore, depletion of p115 in GSCs results in aberrant spindle orientation. Mechanistically, p115 associates with and stabilizes STAT. Finally, ectopic expression of STAT completely restores GSC loss caused by p115 depletion. Collectively, JAK/STAT signaling and p115 form a feedforward loop to maintain male GSC fate. Our work provides new insights into the regulatory mechanism of how stem cell maintenance is properly controlled by JAK/STAT signaling. [Display omitted] •p115, a tER/cis-Golgi golgin protein, is a putative JAK/STAT downstream target•p115-defective male GSCs undergo differentiation•p115 associates with and stabilizes STAT to regulate male GSC maintenance•p115 and JAK/STAT signaling form a feedforward loop to maintain GSC identity In this article, Zhouhua Li and colleagues show that p115 is identified as a downstream target of JAK/STAT signaling in Drosophila testis and is required for the male germline stem cell (GSC) maintenance. p115 associates with and stabilizes Stat92E (STAT) and forms a feedforward loop with JAK/STAT signaling to maintain male GSC fate.