在患有C9orf72突变的ALS和FTD患者中,单细胞转录组和表观基因组发生了不同的变化
Junhao Li1, Manoj K Jaiswal2, Jo-Fan Chien3
1Department of Cognitive Science, University of California San Diego, La Jolla, CA, 92037, US.
Nature communications
|September 15, 2023
概括
C9orf72 (C9) 基因的重复扩张导致ALS和FTD. 这项研究揭示了C9-ALS和C9-FTD脑细胞中明显的分子变化,不同影响神经元和质细胞.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 遗传学 是一个
- 分子生物学分子生物学
背景情况:
- 肌缩侧面硬化症 (ALS) 和前性痴呆症 (FTD) 是神经退行性疾病.
- C9orf72基因的重复扩张是ALS和FTD最常见的遗传原因.
研究的目的:
- 调查与C9orf72基因重复扩张相关的运动和额叶皮层的分子和表观遗传变化.
- 为了区分C9orf72扩张在ALS和FTD中的细胞和区域影响.
主要方法:
- 采用了单核转录组学 (snRNA-seq) 和使用测序 (snATAC-seq) 检测转化酶可访问的染色质的单核测试.
- 对死后脑组织进行了分析,这些脑组织来自患有C9-ALS,C9-FTD和健康对照的人.
主要成果:
- C9-ALS大脑显示广泛的基因表达和染色质可访问性变化,特别是在激发性神经元和星球细胞中,表明蛋白质稳定,新陈代谢和神经元功能的改变,以及星球细胞激活.
- 在C9-FTD大脑中,前额叶皮质的神经元核较少,质细胞的基因表达发生显著变化.
结论:
- 在C9-ALS和C9-FTD中的分子干扰是取决于背景的,根据细胞类型,大脑区域和疾病而异.
- 这些发现提供了关于C9orf72相关的ALS和FTD背后的独特致病机制的见解.
相关概念视频
01:31Translation
Lesson: Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
01:37Neural Regulation
Digestion begins with a cephalic phase that prepares the digestive system to receive food. When our brain processes visual or olfactory information about food, it triggers impulses in the cranial nerves innervating the salivary glands and stomach to prepare for food.
03:03Amyloid Fibrils
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
01:31Translation
Lesson: Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life