<br>HDAC3 促进支持细胞成熟并维持血睾屏障动态,The FASEB Journal

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HDAC3 促进支持细胞成熟并维持血睾屏障动态
The FASEB Journal ( IF 4.4 ) Pub Date : 2024-03-02 , DOI: 10.1096/fj.202301349rr
Mengrou Liu ₁ , Qing He ₁ , Zihan Yuan ₁ , Niuniu Chen ₁ , Sen Ren ₁ , Qian Du ₁ , Yanfeng Wang ₁ , Shenglin Han ₁ , Chen Xu ₁ , Luyang Lu ₁ , Zheng Sun ₂ , Yongjuan Guan ₃ , Jie Xie ₁ , Yichun Guan ₄ , Lan Ye ₁

Affiliation

生殖细胞发育取决于体细胞支持细胞分化为成熟状态并建立生殖细胞特异性血睾屏障（BTB）的能力。 BTB 结构为减数分裂和减数分裂后生殖细胞提供了免疫屏障，其动态通透性有利于瘦身期前精母细胞通过 BTB 短暂运动进入减数分裂。然而，支持细胞成熟中涉及的调节因素以及 BTB 动力学如何协调生殖细胞发育仍不清楚。在这里，我们发现组蛋白脱乙酰酶 HDAC3 在支持细胞中大量表达，并且定位于细胞质和细胞核中。小鼠支持细胞特异性Hdac3敲除会导致不育，血睾屏障完整性受损，导致生殖细胞无法穿过 BTB，并在幼年睾丸中积聚前瘦素期精母细胞。从机制上讲，核HDAC3调节支持细胞成熟基因的表达程序，细胞质HDAC3与间隙连接蛋白Connexin 43形成复合物，通过调节紧密连接蛋白的分布来调节BTB的完整性和动态。我们的研究结果表明，HDAC3 是促进支持细胞成熟和维持血睾屏障稳态的关键调节因子。

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HDAC3 promotes Sertoli cell maturation and maintains the blood–testis barrier dynamics

Germ cell development depends on the capacity of somatic Sertoli cells to undergo differentiation into a mature state and establish a germ cell-specific blood–testis barrier (BTB). The BTB structure confers an immunological barrier for meiotic and postmeiotic germ cells, and its dynamic permeability facilitates a transient movement of preleptotene spermatocytes through BTB to enter meiosis. However, the regulatory factors involved in Sertoli cell maturation and how BTB dynamics coordinate germ cell development remain unclear. Here, we found a histone deacetylase HDAC3 abundantly expresses in Sertoli cells and localizes in both cytoplasm and nucleus. Sertoli cell-specific Hdac3 knockout in mice causes infertility with compromised integrity of blood–testis barrier, leading to germ cells unable to traverse through BTB and an accumulation of preleptotene spermatocytes in juvenile testis. Mechanistically, nuclear HDAC3 regulates the expression program of Sertoli cell maturation genes, and cytoplasmic HDAC3 forms a complex with the gap junction protein Connexin 43 to modulate the BTB integrity and dynamics through regulating the distribution of tight junction proteins. Our findings identify HDAC3 as a critical regulator in promoting Sertoli cell maturation and maintaining the homeostasis of the blood–testis barrier.

更新日期：2024-03-04

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