Institute of Reproductive Medicine, Medical School, Nantong University, Nantong, 226001, China.
Department of Obstetrics and Gynecology, Affiliated Hospital 2 of Nantong University and First People's Hospital of Nantong City, Nantong, 226001, China.
Stem Cell Res Ther. 2022 Jul 26;13(1):351. doi: 10.1186/s13287-022-03025-5.
Stem cell niche maintains stem cell population identity and is essential for the homeostasis of self-renewal and differentiation in Drosophila testes. However, the mechanisms of CySC lineage signals-mediated soma-germline communications in response to external stimuli are unclear.
Pre-initiation complex functions were evaluated by UAS-Gal4-mediated cell effects. RNA sequencing was conducted in NC and eIF5 siRNA-treated cells. Genetic interaction analysis was used to indicate the relationships between eIF5 and eIF1A/eIF2γ in Drosophila testes.
Here, we demonstrated that in CySCs, translation initiation factor eIF5 mediates cyst cell differentiation and the non-autonomously affected germ cell differentiation process. CySCs lacking eIF5 displayed unbalanced cell proliferation and apoptosis, forming testicular germ cell tumors (TGCTs) during spermatogenesis. eIF5 transcriptional regulation network analysis identified multiple metabolic processes and several key factors that might be involved in germ cell differentiation and TGCT formation. Importantly, knockdown of eIF1A and eIF2γ, key components of pre-initiation complex, mimicked the phenotype of knocking down eIF5 in the stem cell niche of Drosophila testes. Genetic interaction analysis indicated that eIF5 was sufficient to rescue the phenotype of tumorlike structures induced by down-regulating eIF1A or eIF2γ in CySCs.
These findings demonstrated that CySC lineage eIF5, together with eIF1A or eIF2γ, mediates soma-germline communications for the stem cell niche homeostasis in Drosophila testes, providing new insights for the prevention of TGCTs.
干细胞龛维持干细胞群体的身份，对于果蝇睾丸中的自我更新和分化的动态平衡至关重要。然而，CySC 谱系信号介导的对外部刺激的体-生殖细胞通讯的机制尚不清楚。
通过 UAS-Gal4 介导的细胞效应评估起始复合物的功能。在 NC 和 eIF5 siRNA 处理的细胞中进行 RNA 测序。遗传相互作用分析用于指示果蝇睾丸中 eIF5 和 eIF1A/eIF2γ 之间的关系。
在这里，我们证明了在 CySCs 中，翻译起始因子 eIF5 介导了囊泡细胞的分化和非自主影响的生殖细胞分化过程。缺乏 eIF5 的 CySCs 表现出不平衡的细胞增殖和凋亡，在精子发生过程中形成睾丸生殖细胞瘤 (TGCT)。eIF5 转录调控网络分析确定了多个代谢过程和几个可能参与生殖细胞分化和 TGCT 形成的关键因素。重要的是，敲低 eIF1A 和 eIF2γ，起始复合物的关键组成部分，模拟了在果蝇睾丸干细胞龛中敲低 eIF5 的表型。遗传相互作用分析表明，eIF5 足以挽救下调 CySCs 中 eIF1A 或 eIF2γ 诱导的肿瘤样结构的表型。
这些发现表明，CySC 谱系 eIF5 与 eIF1A 或 eIF2γ 一起，介导果蝇睾丸中干细胞龛的体-生殖细胞通讯，为 TGCT 的预防提供了新的见解。
