ArticleNature biotechnology2022
Single-nuclei isoform RNA sequencing unlocks barcoded exon connectivity in frozen brain tissue.
Article in Nature biotechnology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.
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Who cites it
99 citing papers in PubMed, 125 citations in OpenAlex.
- Single-cell splice isoform usage reveals distinct axes of cellular identity and senescence.bioRxiv : the preprint server for biology · 2026Article
- Spatial isoform sequencing at single-cell resolution reveals cell-type-specific spatial isoform variability in multiple brain cell types.Nature methods · 2026Article
- Long-read proteogenomic atlas of human neuronal differentiation reveals isoform diversity informing neurodevelopmental risk mechanisms.Nature communications · 2026Article
- Encrypted immunity mediated by peptides.PLoS biology · 2026Review
- Beyond the gene: isoform diversity as a key contributor to human brain disorders.Current opinion in genetics & development · 2026Review
- Tools and tactics for studying alternative splicing.Nature reviews. Genetics · 2026Review
- Coordinated pre-mRNA processing at the single-transcript level.Trends in genetics : TIG · 2026Review
- The splice of life: an isoform-centric view of disease, technology, and therapeutics.The Journal of clinical investigation · 2026Review
- RNAlater-compatible protocol for nuclei isolation from radical prostatectomy prostate cancer resections, enabling single-nucleus resolution RNA-seq.Scientific reports · 2026Article
- Single-nucleus multiomic atlas of ALS primary motor cortex nominates neuroprotective WDR49-expressing astrocytes.Research square · 2026Article
- Combined single-cell profiling of chromatin-transcriptome and splicing across brain cell types, regions and disease state.Nature biotechnology · 2026Article
- Long-read transcriptomics of purified human cortical cell types exposes glial isoform complexity and disease-relevant transcript architecture.bioRxiv : the preprint server for biology · 2026Article
- Isoform-specific m6A deposition and coordinated splicing shape mammalian transcriptome evolution.Nature communications · 2026Article
- Genetic demultiplexing and transcript start site identification from nanopore sequencing of 10x Genomics multiome libraries.bioRxiv : the preprint server for biology · 2026Article
- BenchDrop-seq: a microfluidics-free platform for benchtop single-cell long-read RNA sequencing.bioRxiv : the preprint server for biology · 2026Article
- RNA isoform diversity, splicing variants and switching in single cells of the Alzheimer's disease brain.Communications biology · 2026Article
- Elucidating the coordination of RNA processing using short-read and long-read RNA-sequencing methods.Nature reviews. Molecular cell biology · 2026Review
- MCC-135 Exerts Antiepileptic and Neuroprotective Effects by Downregulating NCX1 Expression to Decrease Intracellular Calcium Overload in the Hippocampus.CNS neuroscience & therapeutics · 2026Article
- Decoding exon inclusion in the human brain reveals more divergent splicing mechanisms in neurons than glia.Genome biology · 2026Article
- cGAS inhibition delays TDP-43-driven ALS Pathogenesis.bioRxiv : the preprint server for biology · 2026Article
39 more citing papers are in PubMed but not listed here.
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Authors and funding
30 authors at 9 institutions in 4 countries.
Funding
Abstract
Single-nuclei RNA sequencing characterizes cell types at the gene level. However, compared to single-cell approaches, many single-nuclei cDNAs are purely intronic, lack barcodes and hinder the study of isoforms. Here we present single-nuclei isoform RNA sequencing (SnISOr-Seq). Using microfluidics, PCR-based artifact removal, target enrichment and long-read sequencing, SnISOr-Seq increased barcoded, exon-spanning long reads 7.5-fold compared to naive long-read single-nuclei sequencing. We applied SnISOr-Seq to adult human frontal cortex and found that exons associated with autism exhibit coordinated and highly cell-type-specific inclusion. We found two distinct combination patterns: those distinguishing neural cell types, enriched in TSS-exon, exon-polyadenylation-site and non-adjacent exon pairs, and those with multiple configurations within one cell type, enriched in adjacent exon pairs. Finally, we observed that human-specific exons are almost as tightly coordinated as conserved exons, implying that coordination can be rapidly established during evolution. SnISOr-Seq enables cell-type-specific long-read isoform analysis in human brain and in any frozen or hard-to-dissociate sample.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.