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Rac1 在睾丸发育和精子发生过程中对支持细胞功能的独特作用。

Distinct Roles for Rac1 in Sertoli Cell Function during Testicular Development and Spermatogenesis.

机构信息

Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.

Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.

出版信息

Cell Rep. 2020 Apr 14;31(2):107513. doi: 10.1016/j.celrep.2020.03.077.

Abstract

Sertoli cells are supporting cells of the testicular seminiferous tubules, which provide a nurturing environment for spermatogenesis. Adult Sertoli cells are polarized so that they can simultaneously support earlier-stage spermatogenic cells (e.g., spermatogonia) basally and later-stage cells (e.g., spermatids) apically. To test the consequences of disrupting cell polarity in Sertoli cells, we perform a Sertoli-specific conditional deletion of Rac1, which encodes a Rho GTPase required for apicobasal cell polarity. Rac1 conditional knockout adults exhibit spermatogenic arrest at the round spermatid stage, with severe disruption of Sertoli cell polarity, and show increased germline and Sertoli cell apoptosis. Thus, Sertoli Rac1 function is critical for the progression of spermatogenesis but, surprisingly, is dispensable for fetal testicular development, adult maintenance of undifferentiated spermatogonia, and meiotic entry. Our data indicate that Sertoli Rac1 function is required only for certain aspects of spermatogenesis and reveal that there are distinct requirements for cell polarity during cellular differentiation.

摘要

支持细胞是睾丸生精小管的支持细胞,为精子发生提供滋养环境。成年支持细胞具有极性,因此它们可以同时在基底侧支持早期阶段的精原细胞(例如精原细胞),并在顶侧支持晚期细胞(例如精细胞)。为了测试破坏支持细胞细胞极性的后果,我们对 Rac1 进行了支持细胞特异性条件性缺失,Rac1 编码了用于顶底细胞极性的 Rho GTPase。Rac1 条件性敲除的成年个体表现出圆形精子细胞阶段的精子发生停滞,支持细胞极性严重破坏,并显示出增加的生殖细胞和支持细胞凋亡。因此,支持细胞 Rac1 功能对于精子发生的进展至关重要,但令人惊讶的是,对于胎儿睾丸发育、未分化精原细胞的成年维持以及减数分裂进入是可有可无的。我们的数据表明,支持细胞 Rac1 功能仅对于精子发生的某些方面是必需的,并揭示了细胞分化过程中细胞极性存在不同的要求。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cc0/7213061/f86030667902/nihms-1584954-f0002.jpg

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