SAT2 regulates Sertoli cell-germline interactions via STIM1-mediated ROS/WNT/β-catenin signaling pathway
SAT2 regulates Sertoli cell-germline interactions via STIM1-mediated ROS/WNT/β-catenin signaling pathway
复制标题
SAT2 通过 STIM1 介导的 ROS/WNT/β-catenin 信号通路调节支持细胞与种系的相互作用。
DOI：
10.1002/cbin.11857
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发表时间：
2022-07-12
影响因子：
3.9
通讯作者：
Zheng, Bo
中科院分区：
文献类型：
--
作者：
Chen, Xia;Zheng, Yanli;Zheng, Bo
支持细胞作为曲细精管的主要组成部分，与生殖细胞紧密接触并产生生态位信号，在精子发生和男性生育中发挥重要作用。然而，在新生小鼠（NM）的睾丸中的支持细胞-生殖系相互作用（SGI）的调节机制在很大程度上仍然不清楚。以前，我们确定亚精胺/精胺N1-乙酰转移酶2（SAT 2）和基质相互作用分子1（STIM 1）是通过比较蛋白质组学分析睾丸索形成的潜在调节剂。在这里，我们证明了SAT 2在NM睾丸发育过程中对SGI的新作用。缺乏SAT 2的睾丸外植体影响支持细胞的错位，但不影响支持细胞的数量，从而导致精原干细胞（SSCs）的维持缺陷。有趣的是，SAT 2是必不可少的迁移TM 4细胞，支持细胞系。从机制上讲，SAT 2能够结合STIM 1，抑制其表达，并调节NM睾丸中活性氧/无翅型（WNT）/β-连环蛋白通路的稳态。总的来说，我们的研究确定，SAT 2能够通过STIM 1介导的WNT信号通路调节SGI。
As the main component of seminiferous tubules, Sertoli cells are in close contact with germ cells and generate niche signals, which exhibit pivotal functions in spermatogenesis and male fertility. However, the regulatory mechanisms of Sertoli cell-germline interactions (SGIs) in the testes of neonatal mice (NM) remain largely unclear. Previously, we identified spermidine/spermine N1-acetyl transferase 2 (SAT2) and stromal interaction molecule 1 (STIM1) to be potential regulators of testicular cord formation via comparative proteomics analysis. Here, we demonstrated a novel role of SAT2 for SGIs during testicular development in NM. Testicular explants lacking SAT2 affected the mislocation, but not the quantity, of Sertoli cells, which led to maintenance defects in spermatogonial stem cells (SSCs). Interestingly, SAT2 was essential for the migration of TM4 cells, a Sertoli cell line. Mechanistically, SAT2 was able to bind STIM1, repress its expression, and regulate homeostasis of a reactive oxygen species/wingless type (WNT)/beta-catenin pathway in NM testes. Collectively, our study identified that SAT2 was able to regulate SGIs via a STIM1-mediated WNT signaling pathway.