相关实验视频

Updated: Sep 8, 2025

Quantitative Analysis of Alternative Pre-mRNA Splicing in Mouse Brain Sections Using RNA In Situ Hybridization Assay

Quantitative Analysis of Alternative Pre-mRNA Splicing in Mouse Brain Sections Using RNA In Situ Hybridization Assay

Published on: August 26, 2018

一个单细胞,长期阅读,异形解决的FTD病例对照研究揭示了人类大脑的细胞类型特异性和广泛的拼接失调

Natan Belchikov¹, Wen Hu², Li Fan³

¹Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA; Center for Neurogenetics, Weill Cornell Medicine, New York, NY, USA; Physiology, Biophysics & Systems Biology Program, Weill Cornell Medicine, New York, NY, USA.

|September 6, 2025

概括

缺血素前性痴呆症 (GRN-FTD) 显示出细胞特异性的拼接变化. 我们的新方法SnISOr-Seq2揭示了隐藏在大量分析中的失调,

科学领域:

神经科学
遗传学
分子生物学

背景情况:

进激素缺陷前性痴呆 (GRN-FTD) 是家族性FTD的主要原因,其特征是TARDNA结合蛋白43 (TDP-43) 病理.
在GRN-FTD中,TDP-43的病理与外失调有关,但其在质细胞和神经元细胞中的细胞特异性仍不明.

研究的目的:

通过一种新的单细胞,长读RNA测序方法,研究GRN-FTD中的细胞特异性外基因失调.
通过批量分析识别被掩盖的剪接变化,并了解它们对神经退行症神经元和质功能的影响.

主要方法:

单核长读RNA测序2 (SnISOr-Seq2) 的开发和应用.
针对3630个高度感兴趣的基因, 实现精确的单细胞分辨率, 在神经退化病例对照研究中.

主要成果:

SnISOr-Seq2显示受FTD相关跳转影响的外显子比含量增加的外显子更短.
在批量分析中,多达30%的细胞分型特异性拼接失调被掩盖,在选择的细胞类型中发生了显著事件.
在GRN-FTD中观察到细胞类型切换和额叶皮层较皮层更大的失调.

结论:

细胞特异性拼接失调是GRN-FTD的一个关键,经常被掩盖的特征.
在单细胞水平上研究神经退行性疾病时,SnISOr-Seq2提供了前所未有的分辨率.
开发的方法在各种大脑疾病和疾病中的拼接缺陷中具有广泛的适用性.

关键词:

CP:神经科学甲基核糖核酸异形一个TDP-43 前性痴呆症前叶退化长时间阅读神经退行症其他类型一个单元一个核接合方式

更多相关视频

A Strategy to Identify de Novo Mutations in Common Disorders such as Autism and Schizophrenia

A Strategy to Identify de Novo Mutations in Common Disorders such as Autism and Schizophrenia

Published on: June 15, 2011

Detection of Alternative Splicing During Epithelial-Mesenchymal Transition

Detection of Alternative Splicing During Epithelial-Mesenchymal Transition

Published on: October 9, 2014

相关概念视频

RNA Splicing

RNA Splicing

Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...

Alternative RNA Splicing

Alternative RNA Splicing

Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...