Cyst stem cell lineage eIF5 non-autonomously prevents testicular germ cell tumor formation via eIF1A/eIF2γ-mediated pre-initiation complex

囊肿干细胞谱系 eIF5 通过 eIF1A/eIF2γ 介导的启动前复合物非自主地阻止睾丸生殖细胞肿瘤的形成

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作者:Zhiran Li #, Yunhao Wu #, Yangbo Fu #, Xia Chen #, Xi Zhao, Xiaolong Wu, Yajuan Lu, Hui He, Cong Shen, Bo Zheng, Jun Yu, Fei Sun

Background

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.

Conclusions

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.

Methods

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.

Results

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. Conclusions: 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.

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