Simultaneous single-cell three-dimensional genome and gene expression profiling uncovers dynamic enhancer connectivity underlying olfactory receptor choice.
Honggui WuJiankun ZhangFanchong JianJinxin Phaedo ChenYinghui ZhengLongzhi TanX Sunney XiePublished in: Nature methods (2024)
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.
Keyphrases
- gene expression
- genome wide
- dna methylation
- single cell
- rna seq
- high resolution
- binding protein
- high throughput
- transcription factor
- resting state
- dna damage
- poor prognosis
- white matter
- induced apoptosis
- multiple sclerosis
- health information
- social media
- decision making
- cell death
- cell proliferation
- cell cycle arrest
- signaling pathway