UCLA

Adult stem cells are crucial for tissue homeostasis and repair. Their fate is tightly regulated by intrinsic genetic factors and extrinsic cues within the stem cell niche. These niches are adaptable, responding to stimuli to maintain homeostasis, but the molecular details of this regulation are not fully understood. This study explores a mechanism that regulates the fate of somatic support cells in the Drosophila testis to maintain tissue homeostasis.The hub in the Drosophila testis niche secretes factors that regulate germline stem cells (GSCs) and cyst stem cells (CySCs). Our lab previously reported that the Snail family transcriptional regulator Escargot (Esg) is necessary for maintaining the identity of both CySCs and hub cells. Depleting esg from hub cells leads to their conversion into CySCs, resulting in the loss of both GSC and CySC populations. Similarly, esg depletion from early somatic cells causes CySCs to differentiate prematurely into daughter cyst cells. These findings indicate that Esg is central to determining somatic cell fates, although the mechanisms are not fully understood. In the adult testis, Egfr activity is low in hub cells under homeostatic conditions but active in CySCs and early cyst cells, regulating their differentiation. Interestingly, Esg protein levels are significantly higher in hub cells than in cyst cells. We hypothesized that Esg influences somatic cell fate by repressing the Egfr signaling cascade. Our results show that repressing Egfr signaling suppresses hub-to-CySC conversion upon esg depletion. Conversely, overexpressing esg in CySCs increases the number of early cyst cells and induces CySC-to-hub cell conversion, which depends on Egfr activity. Constitutive Egfr activation in CySCs prevents this conversion upon esg overexpression. These findings support the hypothesis that Escargot acts upstream of Egfr to regulate somatic cell identity and maintain tissue homeostasis in the testis.