哺乳动物发育障碍的单细胞全胚胎表型
Xingfan Huang1,2, Jana Henck3,4, Chengxiang Qiu1
1Department of Genome Sciences, University of Washington, Seattle, WA, USA.
Nature
|November 15, 2023
概括
整个小鼠胚胎的单细胞RNA测序提供了一个可扩展的方法,用于系统地识别遗传模型中的微妙发育缺陷. 这种方法提供了突变的高分辨率分子和细胞特征,促进了疾病研究.
科学领域:
- 发育生物学
- 遗传学
- 基因组学
背景情况:
- 鼠标模型对于研究人类发育障碍至关重要.
- 传统的表型方法可能会忽略胚胎发育中的微妙缺陷.
- 需要可扩展,高分辨率的方法来描述小鼠遗传模型.
研究的目的:
- 建立整个胚胎单细胞RNA测序作为小鼠遗传模型系统表型化的可扩展平台.
- 能够对小鼠发育障碍进行详细的分子和细胞表征.
- 识别和分析各种突变基因型中的表型差异.
主要方法:
- 基于组合索引的单细胞RNA测序 (scRNA-seq) 的应用
- 在第13.5个胚胎日对来自22个突变型和4个野生型基因型的101个胚胎进行分析 (总数超过160万个核).
- 开发和应用分析框架以检测52种细胞类型/轨迹中的细胞类型组成和基因表达的差异.
主要成果:
- 在22种突变基因型中识别出各种表型效应,影响不同细胞类型和轨迹.
- 野生类型菌株之间的差异的表征和功能增益与丧失突变的比较.
- 在突变者中检测出共享的分子和细胞变化,表明可分解的发育变性.
结论:
- 全胚胎scRNA-seq为小鼠突变的系统分子和细胞表型提供了前所未有的广度和分辨率.
- 这种平台有助于详细描述发育障碍的遗传模型.
- 这种方法有助于理解复杂的遗传相互作用和发育变性.
相关概念视频
01:33Cleavage and Blastulation
51.4K
After a large-single-celled zygote is produced via fertilization, the process of cleavage occurs while zygotes travel through the uterine tube. Cleavage is a mitotic cell division that does not result in growth. With each round of successive cell division, daughter cells get increasingly smaller.
51.4K
01:10Zygotic Development And Stem Cell Formation
7.6K
The development of all multicellular organisms starts with the fusion of haploid cells called sperm and egg to form a diploid zygote. A zygote is a totipotent cell that can develop into a complete organism. The zygote undergoes cell division or cleavage to form an 8-cell mass. Until this stage, the cells are spherical, loosely attached, and remain totipotent. Totipotent cells are capable of developing both the embryonic and the extraembryonic tissues. However, as they continue to divide, they...
7.6K