ArticleProceedings of the National Academy of Sciences of the United States of America2021
Complexity and graded regulation of neuronal cell-type-specific alternative splicing revealed by single-cell RNA sequencing.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.
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Who cites it
56 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
- Curriculum vitae of CUG binding protein 1 (CELF1) in homeostasis and diseases: a systematic review.Cellular & molecular biology letters · 2024Pooled it
- Neurabin I haploinsufficiency disrupts ion channel regulation and synaptic maturation in human cortical neurons in neurodevelopmental disorders.Molecular psychiatry · 2026Article
- Pathological disruption of CELF2 shuttling causes neuronal hyperactivity, learning deficits, and seizures.The Journal of clinical investigation · 2026Article
- Compound models and Pearson residuals for single-cell RNA-seq data without UMIs.Genome biology · 2026Article
- Comprehensive assessment of alternative splicing analysis methods for single-cell RNA-seq.iScience · 2026Article
- Post-transcriptional regulatory networks: The dynamic interplay of RNA-binding proteins.The FEBS journal · 2026Review
- An in vivo parallelized reporter assay to uncover tissue-specific splicing regulatory sequences in a multicellular animal.Nucleic acids research · 2026Article
- Alternative splicing-triggered mRNA decay informs splice-switching targets for neurodevelopmental disorders.The Journal of clinical investigation · 2026Article
- Competition for the conserved branch point sequence influences physiological outcomes in pre-mRNA splicing.eLife · 2026Article
- A neuron type-specific microexon in Ank3/ankyrin-G modulates calcium activity and neuronal excitability.Nature communications · 2026Article
- HDAC Inhibition Reshapes Splicing of Synaptic Plasticity-Related Genes and Neural Network Dynamics.Cellular and molecular neurobiology · 2026Article
- Cell-type-specific alternative splicing in the brain and kidney of a Setbp1S858R Schinzel-Giedion syndrome mouse.Disease models & mechanisms · 2026Article
- MBNL1-dependent alternative splicing promotes neuronal differentiation through regulation of NUMA1 exon 16 during fibroblast-to-neuron reprogramming.Frontiers in cell and developmental biology · 2026Article
- Beyond transcription: RNA-binding proteins steering angiogenesis.American journal of physiology. Heart and circulatory physiology · 2026Review
- High-Resolution Multiplexed Sequencing of Single-Cell Full-length Transcriptome Via Combinational Barcoded Tn5 Transposon Insertion.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A neuron type-specific microexon inbioRxiv : the preprint server for biology · 2025Article
- Article
- Single-nucleus transcriptome atlas of orbitofrontal cortex in ALS with a deep learning-based decoding of alternative polyadenylation mechanisms.Cell genomics · 2025Article
- Article
- Bioinformatics frameworks for single-cell long-read sequencing: unlocking isoform-level resolution.Briefings in bioinformatics · 2025Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
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Abstract
The enormous cellular diversity in the mammalian brain, which is highly prototypical and organized in a hierarchical manner, is dictated by cell-type-specific gene-regulatory programs at the molecular level. Although prevalent in the brain, the contribution of alternative splicing (AS) to the molecular diversity across neuronal cell types is just starting to emerge. Here, we systematically investigated AS regulation across over 100 transcriptomically defined neuronal types of the adult mouse cortex using deep single-cell RNA-sequencing data. We found distinct splicing programs between glutamatergic and GABAergic neurons and between subclasses within each neuronal class. These programs consist of overlapping sets of alternative exons showing differential splicing at multiple hierarchical levels. Using an integrative approach, our analysis suggests that RNA-binding proteins (RBPs) Celf1/2, Mbnl2, and Khdrbs3 are preferentially expressed and more active in glutamatergic neurons, while Elavl2 and Qk are preferentially expressed and more active in GABAergic neurons. Importantly, these and additional RBPs also contribute to differential splicing between neuronal subclasses at multiple hierarchical levels, and some RBPs contribute to splicing dynamics that do not conform to the hierarchical structure defined by the transcriptional profiles. Thus, our results suggest graded regulation of AS across neuronal cell types, which may provide a molecular mechanism to specify neuronal identity and function that are orthogonal to established classifications based on transcriptional regulation.
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Registered trials
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