Single-Cell Joint Profiling of Open Chromatin and Transcriptome by Paired-Seq

Area of Science:

• Genomics
• Molecular Biology
• Cell Biology

Background:

• Understanding cell-type-specific gene regulation is crucial for complex tissues.
• Current methods often lack the throughput for large-scale analysis.
• Simultaneous measurement of chromatin state and gene expression is needed.

Purpose of the Study:

• To develop an ultra-high-throughput method for joint analysis of chromatin accessibility and nuclear transcriptome.
• To enable dissection of cell-type-specific gene regulatory programs in complex biological systems.

Main Methods:

• Paired-seq utilizes a combinatorial barcoding strategy.
• Sequential ligation of multiplexed DNA barcodes to DNA fragments and cDNA.
• High-throughput DNA sequencing and bioinformatic deconvolution of single-cell data.

Main Results:

• Paired-seq achieves joint analysis of open chromatin and nuclear transcriptome from up to one million cells.
• The method provides ultra-high-throughput single-cell multiomics capabilities.
• Enables construction of detailed single-cell multiomic maps.

Conclusions:

• Paired-seq is a powerful tool for dissecting gene regulatory programs.
• Facilitates large-scale single-cell multiomics studies.
• Advances understanding of cellular heterogeneity and function.