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

Authors :
Hagen Tilgner
Simon A. Hardwick
Geoffrey S. Pitt
Man Ying Wong
Andrey D. Prjibelski
Wenjie Luo
Ahmed Mahfouz
Stephen R. Williams
Zachary Bent
Susan Lin
Qi Wang
Adam Frankish
Alexander N. Stein
Bettina Haase
Paul Flicek
Olivier Fedrigo
Christoph Dieterich
Jordan Marrocco
Toby Hunt
Davide Risso
Erich D. Jarvis
August B. Smit
Paul Collier
Jennifer Chew
Steven A. Sloan
Ashley Hayes
Anoushka Joglekar
M. Elizabeth Ross
Neil I. Weisenfeld
Anna Katharina Schlusche
Center for Neurogenomics and Cognitive Research
Amsterdam Neuroscience - Cellular & Molecular Mechanisms
Amsterdam Neuroscience - Neurodegeneration
Source :
Nature Communications, 12(1), Nature Communications, 12(1). NATURE RESEARCH, Joglekar, A, Prjibelski, A, Mahfouz, A, Collier, P, Lin, S, Schlusche, A K, Marrocco, J, Williams, S R, Haase, B, Hayes, A, Chew, J G, Weisenfeld, N I, Wong, M Y, Stein, A N, Hardwick, S A, Hunt, T, Wang, Q, Dieterich, C, Bent, Z, Fedrigo, O, Sloan, S A, Risso, D, Jarvis, E D, Flicek, P, Luo, W, Pitt, G S, Frankish, A, Smit, A B, Ross, M E & Tilgner, H U 2021, ' A spatially resolved brain region-and cell type-specific isoform atlas of the postnatal mouse brain ', Nature Communications, vol. 12, 463, pp. 1-16 . https://doi.org/10.1038/s41467-020-20343-5, Nature Communications, Vol 12, Iss 1, Pp 1-16 (2021), Nature Communications, Nature Communications, 12:463, 1-16. Nature Publishing Group
Publication Year :
2021

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.<br />Alternative RNA splicing varies across the brain. Its mapping at single cell resolution is unclear. Here, the authors provide a spatial and single-cell splicing atlas reporting brain region- and cell type-specific expression of different isoforms in the postnatal mouse brain.

Details

Language :
English
ISSN :
20411723
Database :
OpenAIRE
Journal :
Nature Communications, 12(1), Nature Communications, 12(1). NATURE RESEARCH, Joglekar, A, Prjibelski, A, Mahfouz, A, Collier, P, Lin, S, Schlusche, A K, Marrocco, J, Williams, S R, Haase, B, Hayes, A, Chew, J G, Weisenfeld, N I, Wong, M Y, Stein, A N, Hardwick, S A, Hunt, T, Wang, Q, Dieterich, C, Bent, Z, Fedrigo, O, Sloan, S A, Risso, D, Jarvis, E D, Flicek, P, Luo, W, Pitt, G S, Frankish, A, Smit, A B, Ross, M E & Tilgner, H U 2021, ' A spatially resolved brain region-and cell type-specific isoform atlas of the postnatal mouse brain ', Nature Communications, vol. 12, 463, pp. 1-16 . https://doi.org/10.1038/s41467-020-20343-5, Nature Communications, Vol 12, Iss 1, Pp 1-16 (2021), Nature Communications, Nature Communications, 12:463, 1-16. Nature Publishing Group
Accession number :
edsair.doi.dedup.....7712a28f4e2e541325f3f669a7004ac3
Full Text :
https://doi.org/10.1038/s41467-020-20343-5