PDF(Pubmed)
Abstract：
Testis-specific transcript 10 (Tex10) is a critical factor for pluripotent stem cell maintenance and preimplantation development. Here, we dissect its late developmental roles in primordial germ cell (PGC) specification and spermatogenesis using cellular and animal models. We discover that Tex10 binds the Wnt negative regulator genes, marked by H3K4me3, at the PGC-like cell (PGCLC) stage in restraining Wnt signaling. Depletion and overexpression of Tex10 hyperactivate and attenuate the Wnt signaling, resulting in compromised and enhanced PGCLC specification efficiency, respectively. Using the Tex10 conditional knockout mouse models combined with single-cell RNA sequencing, we further uncover critical roles of Tex10 in spermatogenesis with Tex10 loss causing reduced sperm number and motility associated with compromised round spermatid formation. Notably, defective spermatogenesis in Tex10 knockout mice correlates with aberrant Wnt signaling upregulation. Therefore, our study establishes Tex10 as a previously unappreciated player in PGC specification and male germline development by fine-tuning Wnt signaling.
摘要：
睾丸特异性转录物10（Tex10）是多能干细胞维持和植入前发育的关键因素。这里,我们使用细胞和动物模型剖析其在原始生殖细胞（PGC）规范和精子发生中的晚期发育作用。我们发现Tex10与Wnt负调节基因结合,标记为H3K4me3，在PGC样细胞（PGCLC）阶段抑制Wnt信号。Tex10的耗尽和过表达过度激活和减弱Wnt信号，导致PGCLC规范效率受损和增强，分别。使用Tex10条件敲除小鼠模型结合单细胞RNA测序，我们进一步揭示了Tex10在精子发生中的关键作用，Tex10丢失导致精子数量和运动减少，与受损的圆形精子细胞形成相关。值得注意的是,Tex10基因敲除小鼠精子发生缺陷与异常Wnt信号上调相关。因此,我们的研究通过微调Wnt信号将Tex10确立为PGC规范和雄性生殖系发育中先前未被重视的参与者。
