Evidence map›Paper›PMID 38594596›Full record

ArticleNature neuroscience2024

Single-cell long-read sequencing-based mapping reveals specialized splicing patterns in developing and adult mouse and human brain.

Anoushka Joglekar, Wen Hu, Bei Zhang, Oleksandr Narykov, Mark Diekhans, Jordan Marrocco, Jennifer Balacco, Lishomwa C Ndhlovu, Teresa A Milner, Olivier Fedrigo and 5 more

Open access · hybridAbstract read
In one paragraph

Article in Nature neuroscience, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.

0numbers the graph read from it
0cells of the map it votes in
78citing papers in PubMed
21.5field-weighted citation impact, top 1% of its field
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

78 citing papers in PubMed, 92 citations in OpenAlex.

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18 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

15 authors at 7 institutions in 1 country.

Anoushka JoglekarFeil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.
Wen HuFeil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0002-0604-2119
Bei ZhangSpatial Genomics, Inc., Pasadena, CA, USA.
Oleksandr NarykovBioinformatics and Computational Biology Program, Worcester Polytechnic Institute, Worcester, MA, USA.
Mark DiekhansUC Genomics Institute, University of California, Santa Cruz, Santa Cruz, CA, USA.ORCID http://orcid.org/0000-0002-0430-0989
Jordan MarroccoFeil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0001-8357-5288
Jennifer BalaccoVertebrate Genome Lab, The Rockefeller University, New York, NY, USA.
Lishomwa C NdhlovuFeil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0001-5427-4187
Teresa A MilnerFeil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0002-0458-6569
Olivier FedrigoVertebrate Genome Lab, The Rockefeller University, New York, NY, USA.
Erich D JarvisVertebrate Genome Lab, The Rockefeller University, New York, NY, USA.ORCID http://orcid.org/0000-0001-8931-5049
Gloria SheynkmanDepartment of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA, USA.ORCID http://orcid.org/0000-0002-4223-9947
Dmitry KorkinBioinformatics and Computational Biology Program, Worcester Polytechnic Institute, Worcester, MA, USA.ORCID http://orcid.org/0000-0002-3875-9085
M Elizabeth RossFeil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0001-6440-8089
Hagen U TilgnerFeil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA. hut2006@med.cornell.edu.ORCID http://orcid.org/0000-0002-7058-3606
Cornell University · USRockefeller University · USWorcester Polytechnic Institute · USHoward Hughes Medical Institute · USTouro College · USUniversity of California, Santa Cruz · USUniversity of Virginia · US

Funding

GENCODE Resource ProjectU41HG007234 · NHGRI · SANGER INSTITUTE · PI FLICEK, PAUL · 2013 to 2020
$20.3M
Proteins to Cell SystemsU54NS117170 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ISOM, LORI L., PARENT, JACK M · 2020 to 2024
$11.9M
Contribution of G protein coupled estrogen receptor to changes in hypothalamic plasticity and hypertension susceptibility in mice with accelerated ovarian failureR01HL136520 · NHLBI · WEILL MEDICAL COLL OF CORNELL UNIV · PI MICHAEL J GLASS, Teresa A Milner · 2017 to 2026
$5.0M
Integrative Single Cell isoform and chromatin accessibility Mapping of Chronic Opioid Exposure in Cognitive Brain Areas in HIVU01DA053625 · NIDA · WEILL MEDICAL COLL OF CORNELL UNIV · PI MILNER, TERESA A, NDHLOVU, LISHOMWA C · 2021 to 2025
$4.0M
Progenitor Regulation Underlying Cortical Interneuron SpecificationR01NS105477 · NINDS · WEILL MEDICAL COLL OF CORNELL UNIV · PI ROSS, MARGARET ELIZABETH · 2018 to 2022
$3.1M
Understanding Genetic Complexity in Spina BifidaR01HD111089 · NICHD · WEILL MEDICAL COLL OF CORNELL UNIV · PI RICHARD H. FINNELL, MARGARET ELIZABETH ROSS · 2023 to 2026
$2.8M
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
Multiome measurements connecting transcription start sites at single-nucleotide resolution, DNA methylation and open chromatin status to splicing outcome across single cells in health and diseaseR35GM152101 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI HAGEN ULRICH TILGNER · 2024 to 2026
$1.7M
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
Predicting the functional impact of alternative splicing on protein-protein interactions using an integrated approachR01LM014017 · NLM · WORCESTER POLYTECHNIC INSTITUTE · PI KORKIN, DMITRY, SHEYNKMAN, GLORIA · 2022 to 2025
$1.3M
Developing triazolopyrimidines as novel anti-tubercular agentsR56AI164599 · NIAID · SEATTLE CHILDREN'S HOSPITAL · PI PARISH, TANYA · 2022 to 2022
$492k
Gladstone Institutes (J. David Gladstone Institutes) UM1AI164599NHGRI NIH HHS U41 HG007234NHLBI NIH HHS R01 HL136520NIAID NIH HHS R56 AI164599NICHD NIH HHS R01 HD111089NIDA NIH HHS U01 DA053625NIGMS NIH HHS R01 GM135247NIGMS NIH HHS R35 GM152101NIMH NIH HHS RF1 MH121267NINDS NIH HHS R01 NS105477NINDS NIH HHS U54 NS117170NLM NIH HHS R01 LM014017U.S. Department of Health & Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) R01HD111089U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01-HL136520U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI) U41HG007234U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) 1R01GM135247-01U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) 1RF1MH121267-01U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) 1R01NS105477U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) U54NS117170-04U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA) U01-DA053625U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA) U01 DA053625-01U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA) U01 DA53625U.S. Department of Health & Human Services | NIH | U.S. National Library of Medicine (NLM) R01LM014017
6 · The paper itself

Abstract

RNA isoforms influence cell identity and function. However, a comprehensive brain isoform map was lacking. We analyze single-cell RNA isoforms across brain regions, cell subtypes, developmental time points and species. For 72% of genes, full-length isoform expression varies along one or more axes. Splicing, transcription start and polyadenylation sites vary strongly between cell types, influence protein architecture and associate with disease-linked variation. Additionally, neurotransmitter transport and synapse turnover genes harbor cell-type variability across anatomical regions. Regulation of cell-type-specific splicing is pronounced in the postnatal day 21-to-postnatal day 28 adolescent transition. Developmental isoform regulation is stronger than regional regulation for the same cell type. Cell-type-specific isoform regulation in mice is mostly maintained in the human hippocampus, allowing extrapolation to the human brain. Conversely, the human brain harbors additional cell-type specificity, suggesting gain-of-function isoforms. Together, this detailed single-cell atlas of full-length isoform regulation across development, anatomical regions and species reveals an unappreciated degree of isoform variability across multiple axes.

Indexed as

BrainSingle-Cell AnalysisAlternative SplicingAnimalsHumansMaleMiceMice, Inbred C57BLRNA IsoformsRNA SplicingRNA Isoforms

Identifiers

PMID38594596
PMCPMC11156538
OpenAlexW4394621670

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Registered trials

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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 OpenQuestion graph.