A spatially resolved brain region- and cell type-specific isoform atlas of the postnatal mouse brain

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

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageEnglish
Article number463
JournalNature Communications
Volume12
Issue number1
DOIs
StatePublished - 19 Jan 2021

Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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