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• W4220958064 abstract "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." @default.
• W4220958064 created "2022-04-03" @default.
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• W4220958064 date "2022-03-07" @default.
• W4220958064 modified "2023-10-17" @default.
• W4220958064 title "Single-nuclei isoform RNA sequencing unlocks barcoded exon connectivity in frozen brain tissue" @default.
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• W4220958064 doi "https://doi.org/10.1038/s41587-022-01231-3" @default.
• W4220958064 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35256815" @default.
• W4220958064 hasPublicationYear "2022" @default.
• W4220958064 type Work @default.

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