Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong, China.
Department of Gynecology, the Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, China.
Cell Death Dis. 2021 May 14;12(5):491. doi: 10.1038/s41419-021-03783-9.
Spermatogonia transit-amplifying (TA) divisions are crucial for the differentiation of germline stem cell daughters. However, the underlying mechanism is largely unknown. In the present study, we demonstrated that CG6015 was essential for spermatogonia TA-divisions and elongated spermatozoon development in Drosophila melanogaster. Spermatogonia deficient in CG6015 inhibited germline differentiation leading to the accumulation of undifferentiated cell populations. Transcriptome profiling using RNA sequencing indicated that CG6015 was involved in spermatogenesis, spermatid differentiation, and metabolic processes. Gene Set Enrichment Analysis (GSEA) revealed the relationship between CG6015 and the epidermal growth factor receptor (EGFR) signaling pathway. Unexpectedly, we discovered that phosphorylated extracellular regulated kinase (dpERK) signals were activated in germline stem cell (GSC)-like cells after reduction of CG6015 in spermatogonia. Moreover, Downstream of raf1 (Dsor1), a key downstream target of EGFR, mimicked the phenotype of CG6015, and germline dpERK signals were activated in spermatogonia of Dsor1 RNAi testes. Together, these findings revealed a potential regulatory mechanism of CG6015 via EGFR signaling during spermatogonia TA-divisions in Drosophila testes.
精原细胞过渡扩增（TA）分裂对于生殖干细胞后代的分化至关重要。然而，其潜在的机制在很大程度上尚不清楚。在本研究中，我们证明了 CG6015 对于果蝇的精原细胞 TA 分裂和精子伸长发育是必需的。缺乏 CG6015 的精原细胞抑制了生殖细胞的分化，导致未分化细胞群体的积累。使用 RNA 测序进行的转录组谱分析表明，CG6015 参与了精子发生、精细胞分化和代谢过程。基因集富集分析（GSEA）揭示了 CG6015 与表皮生长因子受体（EGFR）信号通路之间的关系。出乎意料的是，我们发现 CG6015 在精原细胞中减少后，生殖干细胞（GSC）样细胞中的磷酸化细胞外调节激酶（dpERK）信号被激活。此外，raf1 的下游（Dsor1），EGFR 的关键下游靶标，模拟了 CG6015 的表型，并且在 Dsor1 RNAi 睾丸的精原细胞中激活了生殖细胞 dpERK 信号。总之，这些发现揭示了 CG6015 通过果蝇睾丸精原细胞 TA 分裂期间的 EGFR 信号传递的潜在调控机制。
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