High-resolution spatial multi-omics reveals cell-type specific nuclear compartments
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1045287 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26949755_1.fastq.gz | Fastqsanger.gz | |||
| SRR26949755_2.fastq.gz | Fastqsanger.gz | |||
| SRR26949756_1.fastq.gz | Fastqsanger.gz | |||
| SRR26949756_2.fastq.gz | Fastqsanger.gz | |||
| SRR26949757_1.fastq.gz | Fastqsanger.gz |
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Project description:The mammalian nucleus is compartmentalized by diverse subnuclear structures. These subnuclear structures, marked by nuclear bodies and histone modifications, are often cell-type specific and affect gene regulation and 3D genome organization1-3. Understanding nuclear organization requires identifying the molecular constituents of subnuclear structures and mapping their associations with specific genomic loci in individual cells, within complex tissues. Here, we introduce two-layer DNA seqFISH+, which allows simultaneous mapping of 100,049 genomic loci, together with nascent transcriptome for 17,856 genes and a diverse set of immunofluorescently labeled subnuclear structures all in single cells in cell lines and adult mouse cerebellum. Using these multi-omics datasets, we showed that repressive chromatin compartments are more variable by cell type than active compartments. We also discovered a single exception to this rule: an RNA polymerase II (RNAPII)-enriched compartment was associated with long, cell-type specific genes (> 200kb), in a manner distinct from nuclear speckles. Further, our analysis revealed that cell-type specific facultative and constitutive heterochromatin compartments marked by H3K27me3 and H4K20me3 are enriched at specific genes and gene clusters, respectively, and shape radial chromosomal positioning and inter-chromosomal interactions in neurons and glial cells. Together, our results provide a single-cell high-resolution multi-omics view of subnuclear compartments, associated genomic loci, and their impacts on gene regulation, directly within complex tissues.
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