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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Joglekar, A; Prjibelski, A; Mahfouz, A; Collier, P; Lin, S; Schlusche, AK; Marrocco, J; Williams, SR; Haase, B; Hayes, A; Chew, JG; Weisenfeld, NI; Wong, MY; Stein, AN; Hardwick, SA; Hunt, T; Wang, Q; Dieterich, C; Bent, Z; Fedrigo, O; Sloan, SA; Risso, D; Jarvis, ED; Flicek, P; Luo, W; Pitt, GS; Frankish, A; Smit, AB; Ross, ME; Tilgner, HU

Published Date

  • January 19, 2021

Published In

Volume / Issue

  • 12 / 1

Start / End Page

  • 463 -

PubMed ID

  • 33469025

Pubmed Central ID

  • PMC7815907

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-020-20343-5

Language

  • eng

Conference Location

  • England