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GAGE-seq concurrently profiles multiscale 3D genome organization and gene expression in single cells
Tianming Zhou1, Ruochi Zhang1,2, Deyong Jia3
1Ray and Stephanie Lane Computational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA, USA.
Nature Genetics
|May 14, 2024
Summary
A new method, genome architecture and gene expression by sequencing (GAGE-seq), simultaneously measures 3D genome structure and gene expression in single cells. This reveals how genome organization influences cell-specific gene activity.
Area of Science:
- Genomics
- Molecular Biology
- Cell Biology
Background:
- Mammalian genomes possess a complex 3D architecture.
- The functional role of this 3D genome organization is not fully understood.
- Existing single-cell technologies cannot simultaneously profile genome organization and gene expression.
Purpose of the Study:
- To introduce a novel single-cell co-assay, GAGE-seq, for simultaneous measurement of 3D genome structure and transcriptome.
- To investigate the relationship between 3D genome organization and gene expression in specific cell types.
- To explore the functional implications of genome architecture on cell-type-specific gene regulation.
Main Methods:
- Development and application of genome architecture and gene expression by sequencing (GAGE-seq).
- Single-cell co-assay for simultaneous profiling of 3D genome structure and gene expression.
- Application to mouse brain cortex and human bone marrow CD34+ cells.
- Integration with spatial transcriptomic data.
Main Results:
- GAGE-seq successfully characterized the interplay between 3D genome organization and gene expression.
- Multiscale 3D genome features were found to inform cell-type-specific gene expression.
- Regulatory elements were linked to their target genes through 3D genome structure.
- In situ 3D genome variations were identified in the mouse cortex.
- Discordant changes between 3D genome organization and gene expression were observed in human hematopoiesis.
Conclusions:
- GAGE-seq is a scalable, robust, and cost-effective method for single-cell analysis of genome structure and gene expression.
- The study highlights the intricate, cell-type-specific relationships between 3D genome architecture and gene activity.
- Findings underscore a complex, temporal interplay between genome organization and gene expression at the single-cell level.
- GAGE-seq offers a powerful tool for advancing research in diverse biological contexts.
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