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| Status |
Public on Mar 27, 2024 |
| Title |
Concurrent profiling of multiscale 3D genome organization and gene expression in single mammalian cells |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Other
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| Summary |
The organization of mammalian genomes within the nucleus features a complex, multiscale three-dimensional (3D) architecture. The functional significance of these 3D genome features, however, remains largely elusive due to limited single-cell technologies that can concurrently profile genome organization and transcriptional activities. Here, we report GAGE-seq, a highly scalable, robust single-cell co-assay that simultaneously measures 3D genome structure and transcriptome within the same cell. Employing GAGE-seq on mouse brain cortex and human bone marrow CD34+ cells, we comprehensively characterized the intricate relationships between 3D genome and gene expression. We found that these multiscale 3D genome features collectively inform cell type-specific gene expressions, hence contributing to defining cell identity at the single-cell level. Integration of GAGE-seq data with spatial transcriptomic data revealed in situ variations of the 3D genome in mouse cortex. Moreover, our observations of lineage commitment in normal human hematopoiesis unveiled notable discordant changes between 3D genome organization and gene expression, underscoring a complex, temporal interplay at the single-cell level that is more nuanced than previously appreciated. Together, GAGE-seq provides a powerful, cost-effective approach for interrogating genome structure and gene expression relationships at the single-cell level across diverse biological contexts.
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| Overall design |
GAGE-seq of cell lines (K562, GM12878, NIH3T3 and MDS-L) and primary tissues (mouse brain cortex and human bone marrow CD34+ cells)
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| Contributor(s) |
Ma J, Duan Z, Zhou T |
| Citation(s) |
38744973 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R01 HG012303 |
Computational methods for studying single-cell 3D genome |
CARNEGIE MELLON UNIVERSITY |
Zhijun Duan |
| R01 HG012303 |
Computational methods for studying single-cell 3D genome |
CARNEGIE MELLON UNIVERSITY |
Jian Ma |
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| |
| Submission date |
Jul 21, 2023 |
| Last update date |
May 24, 2024 |
| Contact name |
Jian Ma |
| E-mail(s) |
jianma@cs.cmu.edu
|
| Organization name |
Carnegie Mellon University
|
| Street address |
5000 Forbes Ave
|
| City |
Pittsburgh |
| ZIP/Postal code |
15213 |
| Country |
USA |
| |
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| Platforms (3) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
| GPL25526 |
Illumina NovaSeq 6000 (Homo sapiens; Mus musculus) |
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| Samples (18)
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| Relations |
| BioProject |
PRJNA997359 |
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