RNA splicing programs define tissue compartments and cell types at single-cell resolution.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34515025.
- Also identified by DOI 10.7554/eLife.70692 and PMC identifier 8563012.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The extent splicing is regulated at single-cell resolution has remained controversial due to both available data and methods to interpret it. We apply the SpliZ, a new statistical approach, to detect cell-type-specific splicing in >110K cells from 12 human tissues. Using 10X Chromium data for discovery, 9.1% of genes with computable SpliZ scores are cell-type-specifically spliced, including ubiquitously expressed genes <i>MYL6</i> and <i>RPS24</i>. These results are validated with RNA FISH, single-cell PCR, and Smart-seq2. SpliZ analysis reveals 170 genes with regulated splicing during human spermatogenesis, including examples conserved in mouse and mouse lemur. The SpliZ allows model-based identification of subpopulations indistinguishable based on gene expression, illustrated by subpopulation-specific splicing of classical monocytes involving an ultraconserved exon in <i>SAT1</i>. Together, this analysis of differential splicing across multiple organs establishes that splicing is regulated cell-type-specifically.
Medical subject headings
- Cheirogaleidae
- Mice
- RNA Splicing
- Single-Cell Analysis