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

Publication ,  Journal Article
Joglekar, A; Prjibelski, A; Mahfouz, A; Collier, P; Lin, S; Schlusche, AK; Marrocco, J; Williams, SR; Haase, B; Hayes, A; Chew, JG; Wong, MY ...
Published in: Nat Commun
January 19, 2021

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.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

January 19, 2021

Volume

12

Issue

1

Start / End Page

463

Location

England

Related Subject Headings

  • Spatial Analysis
  • Single-Cell Analysis
  • Protein Isoforms
  • Prefrontal Cortex
  • Models, Animal
  • Mice
  • Hippocampus
  • Gene Expression Regulation, Developmental
  • Female
  • Computational Biology
 

Citation

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Joglekar, A., Prjibelski, A., Mahfouz, A., Collier, P., Lin, S., Schlusche, A. K., … Tilgner, H. U. (2021). A spatially resolved brain region- and cell type-specific isoform atlas of the postnatal mouse brain. Nat Commun, 12(1), 463. https://doi.org/10.1038/s41467-020-20343-5
Joglekar, Anoushka, Andrey Prjibelski, Ahmed Mahfouz, Paul Collier, Susan Lin, Anna Katharina Schlusche, Jordan Marrocco, et al. “A spatially resolved brain region- and cell type-specific isoform atlas of the postnatal mouse brain.Nat Commun 12, no. 1 (January 19, 2021): 463. https://doi.org/10.1038/s41467-020-20343-5.
Joglekar A, Prjibelski A, Mahfouz A, Collier P, Lin S, Schlusche AK, et al. A spatially resolved brain region- and cell type-specific isoform atlas of the postnatal mouse brain. Nat Commun. 2021 Jan 19;12(1):463.
Joglekar, Anoushka, et al. “A spatially resolved brain region- and cell type-specific isoform atlas of the postnatal mouse brain.Nat Commun, vol. 12, no. 1, Jan. 2021, p. 463. Pubmed, doi:10.1038/s41467-020-20343-5.
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. A spatially resolved brain region- and cell type-specific isoform atlas of the postnatal mouse brain. Nat Commun. 2021 Jan 19;12(1):463.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

January 19, 2021

Volume

12

Issue

1

Start / End Page

463

Location

England

Related Subject Headings

  • Spatial Analysis
  • Single-Cell Analysis
  • Protein Isoforms
  • Prefrontal Cortex
  • Models, Animal
  • Mice
  • Hippocampus
  • Gene Expression Regulation, Developmental
  • Female
  • Computational Biology