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研究揭示嗅觉受体选择背后的动态增强子连通性
作者:小柯机器人 发布时间:2024/4/18 16:47:13

北京大学谢晓亮等研究人员合作发现,单细胞三维基因组和基因表达谱同布分析揭示,嗅觉受体选择背后的动态增强子连通性。2024年4月15日出版的《自然—方法学》发表了这项成果。

研究人员报道了“连接mRNA与染色质结构(LiMCA)”技术,它能以极高的灵敏度和低投入材料联合剖析三维基因组和转录组。结合LiMCA和高分辨率scATAC-seq检测方法METATAC,研究人员成功地描述了染色质可及性,以及单个发育中嗅觉神经元的成对三维基因组结构和基因表达信息。
 
研究人员扩大了已知嗅觉受体(OR)增强子的范围,并发现了意想不到的增强子动态规律: 嗅觉受体基因及其增强子在早期分化过程中最容易获得。
 
此外,研究人员还揭示了OR逐步表达背后OR与增强子之间的动态空间关系。这些发现为人们提供了宝贵的见解,让人们了解OR和增强子的三维连接是如何动态协调“一个神经元一个受体”的选择过程。

据了解,同时测量单个细胞的3D基因组结构和基因表达,对于理解基因组的结构-功能关系至关重要,但这对现有方法来说具有挑战性。

附:英文原文

Title: Simultaneous single-cell three-dimensional genome and gene expression profiling uncovers dynamic enhancer connectivity underlying olfactory receptor choice

Author: Wu, Honggui, Zhang, Jiankun, Jian, Fanchong, Chen, Jinxin Phaedo, Zheng, Yinghui, Tan, Longzhi, Sunney Xie, X.

Issue&Volume: 2024-04-15

Abstract: The simultaneous measurement of three-dimensional (3D) genome structure and gene expression of individual cells is critical for understanding a genome’s structure–function relationship, yet this is challenging for existing methods. Here we present ‘Linking mRNA to Chromatin Architecture (LiMCA)’, which jointly profiles the 3D genome and transcriptome with exceptional sensitivity and from low-input materials. Combining LiMCA and our high-resolution scATAC-seq assay, METATAC, we successfully characterized chromatin accessibility, as well as paired 3D genome structures and gene expression information, of individual developing olfactory sensory neurons. We expanded the repertoire of known olfactory receptor (OR) enhancers and discovered unexpected rules of their dynamics: OR genes and their enhancers are most accessible during early differentiation. Furthermore, we revealed the dynamic spatial relationship between ORs and enhancers behind stepwise OR expression. These findings offer valuable insights into how 3D connectivity of ORs and enhancers dynamically orchestrate the ‘one neuron–one receptor’ selection process.

DOI: 10.1038/s41592-024-02239-0

Source: https://www.nature.com/articles/s41592-024-02239-0

期刊信息

Nature Methods:《自然—方法学》,创刊于2004年。隶属于施普林格·自然出版集团,最新IF:47.99
官方网址:https://www.nature.com/nmeth/
投稿链接:https://mts-nmeth.nature.com/cgi-bin/main.plex