Simultaneous single-cell three-dimensional genome and gene expression profiling uncovers dynamic enhancer...

Area of Science:

• Genomics
• Molecular Biology
• Neuroscience

Background:

• Simultaneously measuring 3D genome structure and gene expression in single cells is crucial for understanding genome function.
• Existing methods face challenges in sensitivity and input requirements.

Purpose of the Study:

• To present a novel method, Linking mRNA to Chromatin Architecture (LiMCA), for joint profiling of 3D genome and transcriptome.
• To characterize chromatin accessibility, 3D genome structure, and gene expression in developing olfactory sensory neurons.

Main Methods:

• Developed and applied Linking mRNA to Chromatin Architecture (LiMCA) for sensitive, low-input joint profiling.
• Integrated LiMCA with high-resolution single-cell Assay for Transposase-Accessible Chromatin sequencing (scATAC-seq) via METATAC.

Main Results:

• Successfully characterized chromatin accessibility, 3D genome structure, and gene expression in individual developing olfactory sensory neurons.
• Identified novel olfactory receptor (OR) enhancers and their dynamic accessibility during early differentiation.
• Revealed dynamic spatial relationships between ORs and enhancers governing stepwise OR expression.

Conclusions:

• LiMCA provides a sensitive tool for simultaneous 3D genome and transcriptome profiling.
• Dynamic 3D genome architecture of ORs and enhancers orchestrates the 'one neuron-one receptor' selection process.