Human Monocytes - CD14, CD16 - Ziegler-Heitbrock

Contact

RNA splicing programs define tissue compartments and cell types at single cell resolution.

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 data for discovery, 9.1% of genes with computable SpliZ scores are cell-type-specifically spliced, including ubiquitously expressed genes MYL6 and RPS24. 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 SAT1. Together, this analysis of differential splicing across multiple organs establishes that splicing is regulated cell-type-specifically.

Authors: Olivieri JE, Dehghannasiri R, Wang PL, Jang S, de Morree A, Tan SY, Ming J, Ruohao Wu A, Tabula Sapiens Consortium, Quake SR, Krasnow MA, Salzman J,
Journal: Elife;20210913; 10. doi:10.7554/eLife.70692
Year: 2021
PubMed: PMID: 34515025 (Go to PubMed)