单细胞脑器官查发现自闭症发育缺陷
Chong Li1, Jonas Simon Fleck2, Catarina Martins-Costa3
1Institute of Molecular Biotechnology of the Austrian Academy of Science (IMBA), Vienna, Austria. chong.li@imba.oeaw.ac.at.
Nature
|September 13, 2023
概括
我们开发了一个基于CRISPR的系统来选与自闭症相关的基因, 这种方法确定了受这些突变影响的脆弱细胞类型和基因网络.
科学领域:
- 神经科学
- 遗传学
- 发育生物学
背景情况:
- 人类大脑的发展有独特的过程,
- 大脑器官在人类环境中提供了研究这些疾病的模型.
研究的目的:
- 开发一种高通量查系统,用于识别导致神经发育障碍的基因.
- 研究扰乱自闭症谱系障碍相关基因对人类大脑器官发育的影响.
主要方法:
- 开发了CRISPR-人类器官单细胞RNA测序 (CHOOSE) 系统,用于聚合功能丧失的查.
- 使用可诱导的CRISPR-Cas9用于马赛克有机体中的遗传破坏和单细胞转录组.
- 从单细胞转录和染色质数据构建了一个发育基因调节网络.
主要成果:
- 36个高风险自闭症谱系疾病基因的乱显示出对细胞命运的影响.
- 脊椎中间前代,腹前代和上层刺激神经元被确定为易受伤害的细胞类型.
- 破坏BAF染色体重塑复合体的ARID1B亚单元影响了前代细胞命运过渡.
结论:
- 通过CHOOSE系统,可以在有机体模型中有效选疾病易感基因.
- 这项研究确定了神经发育障碍所涉及的关键细胞类型和基因调控网络.
- 这些发现为有机系统中高通量基因的表型特征提供了基础.
相关概念视频
Neurulation
40.2K
Neurulation is the embryological process which forms the precursors of the central nervous system and occurs after gastrulation has established the three primary cell layers of the embryo: ectoderm, mesoderm, and endoderm. In humans, the majority of this system is formed via primary neurulation, in which the central portion of the ectoderm—originally appearing as a flat sheet of cells—folds upwards and inwards, sealing off to form a hollow neural tube. As development proceeds, the...
40.2K
Alzheimer Disease l: Introduction
21
Alzheimer disease is a chronic, progressive, and irreversible neurodegenerative disorder and the most common cause of dementia in older adults. It leads to gradual neuronal loss, causing cognitive decline, behavioral changes, and loss of functional independence.Risk Factors and EtiologyThe disease is multifactorial. Age is the strongest risk factor, with prevalence doubling every 5 years after age 65. Genetic factors include mutations in genes such as APP, PSEN1, and PSEN2, which are associated...
21
Dementia l: Introduction
35
Dementia is an acquired, progressive syndrome characterized by a decline in multiple cognitive domains severe enough to impair daily functioning and reduce independence. Although memory loss is a central feature, the diagnosis requires additional deficits involving language, executive function, visuospatial skills, judgment, calculation, or abstract reasoning. These cognitive impairments reflect underlying neurodegenerative or vascular processes that gradually disrupt neuronal networks...
35


