通过单细胞转录基因分析来解读密码化中精子发生失败的病变发生
Xiaoyan Wang1, Qiang Liu2, Ziyan Zhuang3
1Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China.
Cell reports. Medicine
|September 3, 2024
概括
不下降的丸 (cryptorchidism) 通过影响精子干细胞,损害精子生产. 激活的巨细胞有助于丸损伤和纤维化,提供新的诊断和治疗点.
科学领域:
- 生殖生物学 生殖生物学
- 免疫学 免疫学 免疫学
- 细胞和分子医学是细胞和分子医学.
背景情况:
- 密码症,或未下降的丸,影响1%-9%的男性新生儿,增加不孕症和丸癌症的风险.
- 在密症中男性不孕不育的确切机制尚未完全理解.
- 了解密码体的细胞和分子基础对于开发有效的治疗方法至关重要.
研究的目的:
- 为了研究成年男性丸细胞的单细胞转录组景观,具有密码性.
- 为了确定细胞参与者和分子途径,涉及到密码学相关的不孕症和丸病理.
- 探索免疫细胞,特别是巨细胞在密码体病发病的作用.
主要方法:
- 单细胞RNA测序 (scRNA-seq) 的46,644个丸细胞从成年男性与密码和健康的对照.
- 对基因表达特征进行比较分析,以确定差异表达的基因和细胞功能.
- 在丸组织和精液等离子体中评估瘤细胞激活标记物和分泌蛋白质.
主要成果:
- 密码体的精子生成缺陷与受损的精子体自我更新和分化有关.
- 在患有密码症的个体的丸中观察到激活的巨细胞和它们的脱粒.
- 乳腺细胞通过转化生长因子β1 (TGF-β1) 和cathepsin G的分泌促进间歇性纤维化.
- 精液等离子体中瘤细胞分泌蛋白质的水平升高与丸纤维化在密码症中相关.
结论:
- 密码化症相关的不孕症源于精子干细胞的失调.
- 巨细胞的激活和脱粒化在丸纤维化和密症的发病过程中起着重要作用.
- 对分泌蛋白质的精液等离子体分析可以作为丸细胞激活和丸纤维化在密码症中的生物标志物.
- 这些发现为改善诊断和针对性治疗密码症提供了洞察力.
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