A spatially resolved brain region- and cell type-specific isoform atlas of the postnatal mouse brain.
IF: 17.694
Cited by: 83


Splicing varies across brain regions, but the single-cell resolution of regional variation is unclear. We present a single-cell investigation of differential isoform expression (DIE) between brain regions using single-cell long-read sequencing in mouse hippocampus and prefrontal cortex in 45 cell types at postnatal day 7 ( www.isoformAtlas.com ). Isoform tests for DIE show better performance than exon tests. We detect hundreds of DIE events traceable to cell types, often corresponding to functionally distinct protein isoforms. Mostly, one cell type is responsible for brain-region specific DIE. However, for fewer genes, multiple cell types influence DIE. Thus, regional identity can, although rarely, override cell-type specificity. Cell types indigenous to one anatomic structure display distinctive DIE, e.g. the choroid plexus epithelium manifests distinct transcription-start-site usage. Spatial transcriptomics and long-read sequencing yield a spatially resolved splicing map. Our methods quantify isoform expression with cell-type and spatial resolution and it contributes to further our understanding of how the brain integrates molecular and cellular complexity.


Spatial Transcriptomics

MeSH terms

Alternative Splicing
Animals, Newborn
Computational Biology
Gene Expression Regulation, Developmental
Models, Animal
Prefrontal Cortex
Protein Isoforms
Single-Cell Analysis
Spatial Analysis


Joglekar, Anoushka
Prjibelski, Andrey
Mahfouz, Ahmed
Collier, Paul
Lin, Susan
Schlusche, Anna Katharina
Marrocco, Jordan
Williams, Stephen R
Haase, Bettina
Hayes, Ashley
Chew, Jennifer G
Weisenfeld, Neil I
Wong, Man Ying
Stein, Alexander N
Hardwick, Simon A
Hunt, Toby
Wang, Qi
Dieterich, Christoph
Bent, Zachary
Fedrigo, Olivier
Sloan, Steven A
Risso, Davide
Jarvis, Erich D
Flicek, Paul
Luo, Wenjie
Pitt, Geoffrey S
Frankish, Adam
Smit, August B
Ross, M Elizabeth
Tilgner, Hagen U

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