Evidence map›Paper›PMID 33469025›Full record

ArticleNature communications2021

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 and 20 more

Abstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 146 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
146citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

146 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Targeted Mechanogenetics to Modulate Specific Deep Neural Circuits.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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86 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

30 authors.

Anoushka JoglekarBrain and Mind Research Institute and Center for Neurogenetics, Weill Cornell Medicine, New York, NY, USA.ORCID 0000-0002-7818-6867
Andrey PrjibelskiCenter for Algorithmic Biotechnology, Institute of Translational Biomedicine, St. Petersburg State University, St Petersburg, Russia.
Ahmed MahfouzDepartment of Human Genetics, Leiden University Medical Center, Leiden, 2333 ZC, The Netherlands.
Paul CollierBrain and Mind Research Institute and Center for Neurogenetics, Weill Cornell Medicine, New York, NY, USA.
Susan LinGraduate Program in Neuroscience, Weill Cornell Medical College, 1300 York Avenue, New York, NY, 10065, USA.ORCID 0000-0001-9344-6594
Anna Katharina SchluscheBrain and Mind Research Institute and Center for Neurogenetics, Weill Cornell Medicine, New York, NY, USA.
Jordan MarroccoHarold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, New York, NY, USA.ORCID 0000-0001-8357-5288
Stephen R Williams10x Genomics, Pleasanton, CA, USA.
Bettina HaaseThe Vertebrate Genomes Lab, The Rockefeller University, New York, NY, USA.
Ashley Hayes10x Genomics, Pleasanton, CA, USA.
Jennifer G Chew10x Genomics, Pleasanton, CA, USA.
Neil I Weisenfeld10x Genomics, Pleasanton, CA, USA.
Man Ying WongBrain and Mind Research Institute and Appel Alzheimer's Research Institute, Weill Cornell Medicine, New York, NY, USA.
Alexander N SteinSchool of General Studies, Columbia University, New York, NY, USA.
Simon A HardwickBrain and Mind Research Institute and Center for Neurogenetics, Weill Cornell Medicine, New York, NY, USA.
Toby HuntEuropean Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, UK.
Qi WangSection of Bioinformatics and Systems Cardiology, University Hospital, 96120, Heidelberg, Germany.
Christoph DieterichSection of Bioinformatics and Systems Cardiology, University Hospital, 96120, Heidelberg, Germany.
Zachary Bent10x Genomics, Pleasanton, CA, USA.
Olivier FedrigoThe Vertebrate Genomes Lab, The Rockefeller University, New York, NY, USA.
Steven A SloanDepartment of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
Davide RissoDepartment of Statistical Sciences, University of Padova, Padova, Italy.
Erich D JarvisThe Vertebrate Genomes Lab, The Rockefeller University, New York, NY, USA.
Paul FlicekEuropean Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, UK.ORCID 0000-0002-3897-7955
Wenjie LuoBrain and Mind Research Institute and Appel Alzheimer's Research Institute, Weill Cornell Medicine, New York, NY, USA.ORCID 0000-0003-3752-8266
Geoffrey S PittGraduate Program in Neuroscience, Weill Cornell Medical College, 1300 York Avenue, New York, NY, 10065, USA.ORCID 0000-0003-2246-0289
Adam FrankishEuropean Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, UK.
August B SmitDepartment of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University, Amsterdam, The Netherlands.
M Elizabeth RossBrain and Mind Research Institute and Center for Neurogenetics, Weill Cornell Medicine, New York, NY, USA.ORCID 0000-0001-6440-8089
Hagen U TilgnerBrain and Mind Research Institute and Center for Neurogenetics, Weill Cornell Medicine, New York, NY, USA. hut2006@med.cornell.edu.ORCID 0000-0002-7058-3606

Funding

GENCODE Resource ProjectU41HG007234 · NHGRI · SANGER INSTITUTE · PI FLICEK, PAUL · 2013 to 2020
$20.3M
Cancer Genomics:Integrative and Scalable Solutions in R / BioconductorU24CA180996 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI MORGAN, MARTIN T, WALDRON, LEVI · 2014 to 2023
$6.9M
Molecular and circuit defects underlying different SCN2A mutations and ASDsR01MH118934 · NIMH · WEILL MEDICAL COLL OF CORNELL UNIV · PI PITT, GEOFFREY S · 2019 to 2023
$3.2M
Progenitor Regulation Underlying Cortical Interneuron SpecificationR01NS105477 · NINDS · WEILL MEDICAL COLL OF CORNELL UNIV · PI ROSS, MARGARET ELIZABETH · 2018 to 2022
$3.1M
Molecular Drivers of Human GliogenesisR01MH125956 · NIMH · EMORY UNIVERSITY · PI SLOAN, STEVEN A · 2021 to 2025
$3.0M
Cross-species conservation of cell-type and single-cell specific isoform expressionR01GM135247 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI TILGNER, HAGEN ULRICH · 2020 to 2023
$2.3M
Multidisciplinary Research Training in Cardiovascular DiseaseT32HL160520 · NHLBI · WEILL MEDICAL COLL OF CORNELL UNIV · PI Geoffrey S Pitt, Jonathan W. Weinsaft · 2022 to 2026
$2.0M
Single cell isoform expression across mouse brain regions and developmentRF1MH121267 · NIMH · WEILL MEDICAL COLL OF CORNELL UNIV · PI TILGNER, HAGEN ULRICH · 2019 to 2019
$1.5M
Genetic and Environmental Influences on AddictionT32DA039080 · NIDA · WEILL MEDICAL COLL OF CORNELL UNIV · PI Teresa A Milner · 2017 to 2026
$1.4M
PHARMACOLOGIC STUDIES OF CNS PAIN MOLULATORY SYSTEMSR01DA003980 · NIDA · UNIVERSITY OF IOWA · PI PROUDFIT, HERBERT K · 1985 to 2003
$1.0M
Howard Hughes Medical InstituteNCI NIH HHS U24 CA180996NHGRI NIH HHS U41 HG007234NHLBI NIH HHS T32 HL160520NIDA NIH HHS R01 DA003980NIDA NIH HHS T32 DA039080NIGMS NIH HHS R01 GM135247NIMH NIH HHS R01 MH118934NIMH NIH HHS R01 MH125956NIMH NIH HHS RF1 MH121267NINDS NIH HHS R01 NS105477Wellcome TrustWellcome Trust WT108749/Z/15/Z
6 · The paper itself

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.

Indexed as

Alternative SplicingAnimalsAnimals, NewbornComputational BiologyFemaleGene Expression Regulation, DevelopmentalHippocampusMiceModels, AnimalPrefrontal CortexProtein IsoformsSingle-Cell AnalysisSpatial AnalysisProtein Isoforms

Identifiers

PMID33469025
PMCPMC7815907

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.