作为一个潜在的候选人,ESX1基因在非阻塞性亚精精子症中负责男性不孕
Agnieszka Malcher1, Zuzanna Graczyk2, Hermann Bauer3
1Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland. agnieszka.malcher@igcz.poznan.pl.
Scientific reports
|October 2, 2023
概括
研究人员使用CRISPRa技术在人类生殖细胞中激活了ESX1基因. 这种激活揭示了可能与男性不育相关的基因网络,为受影响的精子生成提供了新的诊断和治疗点.
科学领域:
- 生殖生物学 生殖生物学
- 遗传学 遗传学 是一个
- 分子生物学分子生物学
背景情况:
- 男性不孕症影响40-50%的不孕夫妇,通常是由于受精的发育受损,导致非阻塞性精子缺血 (NOA).
- 目前尚不完全了解NOA的遗传基础,这阻碍了诊断和治疗.
- 全基因组测序 (WGS) 可以识别与NOA相关的基因中的罕见变异,例如ESX1.1.
研究的目的:
- 研究ESX1基因在男性生殖细胞中的作用.
- 使用CRISPR激活 (CRISPRa) 技术激活人类生殖细胞 (TCam-2) 中的ESX1基因.
- 为了确定ESX1调节的基因,并评估它们在亚精患者中的相关性.
主要方法:
- 采用CRISPR激活 (CRISPRa) 技术,对TCam-2细胞中的ESX1表达进行上调.
- 进行RNA测序 (RNA-seq) 来识别由ESX1.1转录调节的基因.
- 确定关键基因的表达水平在不同精子生成状态的患者队列中得到了验证.
主要成果:
- 与对照细胞相比,TCam-2细胞中成功和显著地激活了ESX1基因 (p < 0.01).
- RNA-seq发现了一个由50多个基因组成的网络,这些基因可能受到ESX1.1的调节.
- 参与细胞增殖和分化的6个基因 (NANOG,CXCR4,RPS6KA5,CCND1,PDE1C,LINC00662) 在阿佐精患者,特别是ESX1突变患者的表达中显示出逆相关性.
结论:
- 通过使用CRISPRa.a在人类生殖细胞中成功激活ESX1基因.
- ESX1调节精子生成至关重要的基因网络.
- 失调ESX1及其下游目标可能会导致男性不孕症和非阻塞性亚精,呈现潜在的生物标志物.
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