生物
生殖细胞
细胞生物学
支持细胞
串扰
RNA剪接
血睾丸屏障
条件基因敲除
精子发生
转录因子
基因
遗传学
表型
内分泌学
核糖核酸
物理
光学
作者
Shenglei Feng,Hui Wen,Kuan Liu,Mengneng Xiong,Jinmei Li,Yiqian Gui,Chunyu Lv,Jin Zhang,Xixiang Ma,Xiaoli Wang,Shuiqiao Yuan
出处
期刊:Development
[The Company of Biologists]
日期:2023-01-31
卷期号:150 (3)
摘要
Spermatogenesis depends on the crosstalk of Sertoli cells (SCs) and germ cells. However, the gene regulatory network establishing the communications between SCs and germ cells remains unclear. Here, we report that heterogeneous nuclear ribonucleoprotein H1 (hnRNPH1) in SCs is essential for the establishment of crosstalk between SCs and germ cells. Conditional knockout of hnRNPH1 in mouse SCs leads to compromised blood-testis barrier function, delayed meiotic progression, increased germ cell apoptosis, sloughing of germ cells and, eventually, infertility of mice. Mechanistically, we discovered that hnRNPH1 could interact with the splicing regulator PTBP1 in SCs to regulate the pre-mRNA alternative splicing of the target genes functionally related to cell adhesion. Interestingly, we also found hnRNPH1 could cooperate with the androgen receptor, one of the SC-specific transcription factors, to modulate the transcription level of a group of genes associated with the cell-cell junction and EGFR pathway by directly binding to the gene promoters. Collectively, our findings reveal a crucial role for hnRNPH1 in SCs during spermatogenesis and uncover a potential molecular regulatory network involving hnRNPH1 in establishing Sertoli-germ cell crosstalk.
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