Single-cell alternative polyadenylation analysis delineates GABAergic neuron types.

Yang, Yang, Paul, Anirban, Bach, Thao Nguyen, Huang, Z Josh, Zhang, Michael Q (July 2021) Single-cell alternative polyadenylation analysis delineates GABAergic neuron types. BMC Biology, 19 (1). p. 144. ISSN 1741-7007

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URL: https://www.ncbi.nlm.nih.gov/pubmed/34301239
DOI: 10.1186/s12915-021-01076-3

Abstract

BACKGROUND: Alternative polyadenylation (APA) is emerging as an important mechanism in the post-transcriptional regulation of gene expression across eukaryotic species. Recent studies have shown that APA plays key roles in biological processes, such as cell proliferation and differentiation. Single-cell RNA-seq technologies are widely used in gene expression heterogeneity studies; however, systematic studies of APA at the single-cell level are still lacking. RESULTS: Here, we described a novel computational framework, SAPAS, that utilizes 3'-tag-based scRNA-seq data to identify novel poly(A) sites and quantify APA at the single-cell level. Applying SAPAS to the scRNA-seq data of phenotype characterized GABAergic interneurons, we identified cell type-specific APA events for different GABAergic neuron types. Genes with cell type-specific APA events are enriched for synaptic architecture and communications. In further, we observed a strong enrichment of heritability for several psychiatric disorders and brain traits in altered 3' UTRs and coding sequences of cell type-specific APA events. Finally, by exploring the modalities of APA, we discovered that the bimodal APA pattern of Pak3 could classify chandelier cells into different subpopulations that are from different laminar positions. CONCLUSIONS: We established a method to characterize APA at the single-cell level. When applied to a scRNA-seq dataset of GABAergic interneurons, the single-cell APA analysis not only identified cell type-specific APA events but also revealed that the modality of APA could classify cell subpopulations. Thus, SAPAS will expand our understanding of cellular heterogeneity.

Item Type: Paper
Subjects: diseases & disorders > mental disorders
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > interneurons > GABAergic interneurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > interneurons > GABAergic interneurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > interneurons > GABAergic interneurons
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression
CSHL Authors:
Communities: CSHL labs > Huang lab
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: 23 July 2021
Date Deposited: 28 Jul 2021 14:14
Last Modified: 02 Aug 2021 18:33
PMCID: PMC8299648
URI: https://repository.cshl.edu/id/eprint/40303

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