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

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

In: Nature Communications, Vol. 12, No. 1, 463, 19.01.2021.

Research output: Contribution to journal › Article › peer-review

Harvard

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 2021, 'A spatially resolved brain region- and cell type-specific isoform atlas of the postnatal mouse brain', Nature Communications, vol. 12, no. 1, 463. https://doi.org/10.1038/s41467-020-20343-5

APA

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., ... Tilgner, H. U. (2021). A spatially resolved brain region- and cell type-specific isoform atlas of the postnatal mouse brain. Nature Communications, 12(1), [463]. https://doi.org/10.1038/s41467-020-20343-5

Vancouver

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. Nature Communications. 2021 Jan 19;12(1). 463. https://doi.org/10.1038/s41467-020-20343-5

Author

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. / A spatially resolved brain region- and cell type-specific isoform atlas of the postnatal mouse brain. In: Nature Communications. 2021 ; Vol. 12, No. 1.

BibTeX

@article{070e4a2657ef4eb9ab4a05659423abf9,

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

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.",

keywords = "Alternative Splicing/physiology, Animals, Animals, Newborn, Computational Biology, Female, Gene Expression Regulation, Developmental/physiology, Hippocampus/cytology, Mice, Models, Animal, Prefrontal Cortex/cytology, Protein Isoforms/analysis, Single-Cell Analysis/methods, Spatial Analysis",

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

year = "2021",

month = jan,

day = "19",

doi = "10.1038/s41467-020-20343-5",

language = "English",

volume = "12",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

RIS

TY - JOUR

T1 - A spatially resolved brain region- and cell type-specific isoform atlas of the postnatal mouse brain

AU - Joglekar, Anoushka

AU - Prjibelski, Andrey

AU - Mahfouz, Ahmed

AU - Collier, Paul

AU - Lin, Susan

AU - Schlusche, Anna Katharina

AU - Marrocco, Jordan

AU - Williams, Stephen R.

AU - Haase, Bettina

AU - Hayes, Ashley

AU - Chew, Jennifer G.

AU - Weisenfeld, Neil I.

AU - Wong, Man Ying

AU - Stein, Alexander N.

AU - Hardwick, Simon A.

AU - Hunt, Toby

AU - Wang, Qi

AU - Dieterich, Christoph

AU - Bent, Zachary

AU - Fedrigo, Olivier

AU - Sloan, Steven A.

AU - Risso, Davide

AU - Jarvis, Erich D.

AU - Flicek, Paul

AU - Luo, Wenjie

AU - Pitt, Geoffrey S.

AU - Frankish, Adam

AU - Smit, August B.

AU - Ross, M. Elizabeth

AU - Tilgner, Hagen U.

PY - 2021/1/19

Y1 - 2021/1/19

N2 - 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.

AB - 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.

KW - Alternative Splicing/physiology

KW - Animals

KW - Animals, Newborn

KW - Computational Biology

KW - Female

KW - Gene Expression Regulation, Developmental/physiology

KW - Hippocampus/cytology

KW - Mice

KW - Models, Animal

KW - Prefrontal Cortex/cytology

KW - Protein Isoforms/analysis

KW - Single-Cell Analysis/methods

KW - Spatial Analysis

UR - http://www.scopus.com/inward/record.url?scp=85099548142&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/e9542866-3324-3e35-9166-72b467fe571d/

U2 - 10.1038/s41467-020-20343-5

DO - 10.1038/s41467-020-20343-5

M3 - Article

C2 - 33469025

AN - SCOPUS:85099548142

VL - 12

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 463

ER -

ID: 76916854