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Single-cell alternative polyadenylation analysis delineates GABAergic neuron types.

Publication ,  Journal Article
Yang, Y; Paul, A; Bach, TN; Huang, ZJ; Zhang, MQ
Published in: BMC Biol
July 23, 2021

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.

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Published In

BMC Biol

DOI

EISSN

1741-7007

Publication Date

July 23, 2021

Volume

19

Issue

1

Start / End Page

144

Location

England

Related Subject Headings

  • p21-Activated Kinases
  • Single-Cell Analysis
  • Sequence Analysis, RNA
  • Polyadenylation
  • Humans
  • GABAergic Neurons
  • Developmental Biology
  • 31 Biological sciences
  • 3' Untranslated Regions
  • 06 Biological Sciences
 

Citation

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Yang, Y., Paul, A., Bach, T. N., Huang, Z. J., & Zhang, M. Q. (2021). Single-cell alternative polyadenylation analysis delineates GABAergic neuron types. BMC Biol, 19(1), 144. https://doi.org/10.1186/s12915-021-01076-3
Yang, Yang, Anirban Paul, Thao Nguyen Bach, Z Josh Huang, and Michael Q. Zhang. “Single-cell alternative polyadenylation analysis delineates GABAergic neuron types.BMC Biol 19, no. 1 (July 23, 2021): 144. https://doi.org/10.1186/s12915-021-01076-3.
Yang Y, Paul A, Bach TN, Huang ZJ, Zhang MQ. Single-cell alternative polyadenylation analysis delineates GABAergic neuron types. BMC Biol. 2021 Jul 23;19(1):144.
Yang, Yang, et al. “Single-cell alternative polyadenylation analysis delineates GABAergic neuron types.BMC Biol, vol. 19, no. 1, July 2021, p. 144. Pubmed, doi:10.1186/s12915-021-01076-3.
Yang Y, Paul A, Bach TN, Huang ZJ, Zhang MQ. Single-cell alternative polyadenylation analysis delineates GABAergic neuron types. BMC Biol. 2021 Jul 23;19(1):144.
Journal cover image

Published In

BMC Biol

DOI

EISSN

1741-7007

Publication Date

July 23, 2021

Volume

19

Issue

1

Start / End Page

144

Location

England

Related Subject Headings

  • p21-Activated Kinases
  • Single-Cell Analysis
  • Sequence Analysis, RNA
  • Polyadenylation
  • Humans
  • GABAergic Neurons
  • Developmental Biology
  • 31 Biological sciences
  • 3' Untranslated Regions
  • 06 Biological Sciences