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分析 Notch1 信号在哺乳动物精子发生中的作用。

Analysis of Notch1 signaling in mammalian sperm development.

机构信息

College of Medicine, School of Medicine and Health Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.

PhD Program in Humanics, School of Integrative and Global Majors, University of Tsukuba, 1- 1-1 Tennodai, Tsukuba, Ibaraki, 305-8577, Japan.

出版信息

BMC Res Notes. 2023 Jun 19;16(1):108. doi: 10.1186/s13104-023-06378-z.

Abstract

OBJECTIVE

A mammalian Delta-Notch signaling component, Notch1, has been suggested for its expression during the normal sperm development although its conditional deletion caused no apparent abnormalities. Since we established our original transgenic mouse system that enabled labeling of past and ongoing Notch1 signaling at a cellular level, we tried to validate that observation in vivo. Our transgenic mouse system used Cre/loxP system to induce tandem dsRed expression upon Notch1 signaling.

RESULTS

To our surprise, we were unable to observe tandem dsRed expression in the seminiferous tubules where the sperms developed. In addition, tandem dsRed expression was lacking in the somatic cells of the next generation in our transgenic mouse system, suggesting that sperms received no Notch1 signaling during their development. To validate this result, we conducted re-analysis of four single-cell RNA-seq datasets from mouse and human testes and showed that Notch1 expression was little in the sperm cell lineage. Collectively, our results posed a question into the involvement of Notch1 in the normal sperm development although this observation may help the interpretation of the previous result that Notch1 conditional deletion caused no apparent abnormalities in murine spermatogenesis.

摘要

目的

尽管条件性缺失 Notch1 并未导致明显的异常,但已有研究提示哺乳动物 Delta-Notch 信号组分 Notch1 在精子正常发育过程中有表达。由于我们建立了原始的转基因小鼠系统,该系统可在细胞水平上对过去和正在进行的 Notch1 信号进行标记,因此我们试图在体内验证这一观察结果。我们的转基因小鼠系统使用 Cre/loxP 系统,在 Notch1 信号诱导时串联表达 dsRed。

结果

令我们惊讶的是,我们无法在精子发生的曲细精管中观察到串联 dsRed 的表达。此外,在我们的转基因小鼠系统中,下一代体细胞中缺乏串联 dsRed 的表达,这表明精子在发育过程中未接收到 Notch1 信号。为了验证这一结果,我们对来自小鼠和人类睾丸的四个单细胞 RNA-seq 数据集进行了重新分析,结果表明 Notch1 在精子细胞谱系中的表达水平较低。综上所述,尽管这一观察结果可能有助于解释 Notch1 条件性缺失在小鼠精子发生中未引起明显异常的先前结果,但我们的结果对 Notch1 是否参与正常精子发生提出了质疑。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18c5/10280896/a504afe5e6df/13104_2023_6378_Fig1_HTML.jpg

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