来自莱迪格细胞的PTN激活SDC2,并通过GFRA1调节人类精子干细胞的增殖和存活
Xueheng Zhao1,2,3, Lvjun Liu1, Zenghui Huang2,3
1Hunan Provincial Key Laboratory of Regional Hereditary Birth Defect Prevention and Control, Changsha Hospital for Maternal & Child Health Care Affiliated to Hunan Normal University, Changsha, Hunan, 410000, China.
Biological research
|September 16, 2024
概括
莱迪格细胞通过类蛋白 (PTN) 和合成素-2 (SDC2) 调节人类精子干细胞 (SSC). 降低PTN/SDC2的调节会损害SSC功能,并与男性不孕症有关.
科学领域:
- 生殖生物学 生殖生物学
- 干细胞生物学 干细胞生物学
- 分子内分泌学分子内分泌学
背景情况:
- 精子干细胞 (SSC) 对男性生育能力至关重要.
- 与小鼠模型相比,人类的SSC调节机制仍然不太了解.
研究的目的:
- 阐明由丸体细胞参与人体SSC调节的信号通路.
- 为了确定治疗男性不孕症的潜在分子标.
主要方法:
- 对单细胞RNA测序数据的分析 (GSE149512,GSE112013).
- 免疫光,STRING预测,蛋白质免疫沉,以及人类SSC线的SDC2敲击试验.
- 转录组分析和外源PTN救援实验.
主要成果:
- 莱迪格细胞通过类蛋白 (PTN) 和合成素-2 (SDC2) 与SSCs进行通信.
- 人类SSC中SDC2的淘汰减少了增殖,DNA合成,PLZF表达和GFRA1水平,同时抑制了HIF-1信号传递.
- 在缺乏SDC2的SSC中,PTN的使用挽救了SDC2的增殖和GFRA1的表达.
- 在非阻塞性亚精子症 (NOA) 患者中观察到PTN和SDC2表达的减少和局部的改变.
结论:
- 确定了一种涉及PTN-SDC2信号传递在丸微环境对人类SSC调节中的新机制.
- 降低PTN和SDC2的调节可能会导致NOA中的精子生成受损.
- PTN-SDC2通路代表了男性不孕症的潜在治疗标.
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