Evidence map›Paper›PMID 40883294›Full record

ArticleNature communications2025

A spatial long-read approach at near-single-cell resolution reveals developmental regulation of splicing and polyadenylation sites in distinct cortical layers and cell types.

Careen Foord, Andrey D Prjibelski, Wen Hu, Lieke Michielsen, Andrea Vandelli, Oleksandr Narykov, Brian Evans, Justine Hsu, Natan Belchikov, Julien Jarroux and 7 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
–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

20 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Review
  5. Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Review
  11. Review
  12. Article
  13. Review
  14. Review
  15. Article
  16. Review
  17. Long-Read Sequencing Reveals RNA Splicing Complexity in Human Diseases.Computational and structural biotechnology journal · 2026
    Review
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Careen Foord *Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0003-2984-834X
Andrey D Prjibelski *Department of Computer Science, University of Helsinki, Helsinki, Finland.
Wen Hu *Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0002-0604-2119
Lieke MichielsenFeil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0003-4615-1309
Andrea VandelliRNA Systems Biology Lab, Center for Human Technologies, Istituto Italiano di Tecnologia, Genova, Italy.ORCID http://orcid.org/0000-0002-8879-0144
Oleksandr NarykovBioinformatics and Computational Biology Program, Worcester Polytechnic Institute, Worcester, MA, USA.
Brian EvansFeil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.
Justine HsuFeil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.
Natan BelchikovFeil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.
Julien JarrouxFeil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0002-7185-6960
Yi HeFeil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.
M Elizabeth RossFeil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0001-6440-8089
Iman HajirasoulihaInstitute for Computational Biomedicine, Department of Physiology and Biophysics, Weill Cornell Medicine of Cornell University, New York, NY, USA.ORCID http://orcid.org/0000-0002-0600-3371
Gian Gaetano TartagliaRNA Systems Biology Lab, Center for Human Technologies, Istituto Italiano di Tecnologia, Genova, Italy.ORCID http://orcid.org/0000-0001-7524-6310
Dmitry KorkinBioinformatics and Computational Biology Program, Worcester Polytechnic Institute, Worcester, MA, USA.ORCID http://orcid.org/0000-0002-3875-9085
Alexandru I TomescuDepartment of Computer Science, University of Helsinki, Helsinki, Finland.ORCID http://orcid.org/0000-0002-5747-8350
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

Funding

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
Tri-Institutional PhD Program in Computational Biology & MedicineT32GM132083 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI Doron Betel, Iman Hajirasouliha · 2020 to 2026
$3.6M
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
Improving Metagenomic Analysis with Novel Algorithms and TechnologiesR35GM138152 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI Iman Hajirasouliha · 2020 to 2026
$2.5M
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
Genetic and Environmental Influences on AddictionT32DA039080 · NIDA · WEILL MEDICAL COLL OF CORNELL UNIV · PI Teresa A Milner · 2017 to 2026
$1.4M
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
EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020) 851093, SAFEBIOEC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020) No. 851093, SAFEBIONational Science Foundation (NSF) GRFP # 2139291NICHD NIH HHS R01 HD111089NIDA NIH HHS T32 DA039080NIDA NIH HHS U01 DA053625NIGMS NIH HHS R01 GM135247NIGMS NIH HHS R35 GM138152NIGMS NIH HHS R35 GM152101NIGMS NIH HHS T32 GM132083NIMH NIH HHS RF1 MH121267NLM NIH HHS R01 LM014017U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01HD111089U.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 General Medical Sciences (NIGMS) MIRA R35 GM152101-01U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA) 2T32DA039080U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA) U01 DA053625-01U.S. Department of Health & Human Services | NIH | U.S. National Library of Medicine (NLM) 1R01LM014017-01
6 · The paper itself

Abstract

Genome-wide spatial long-read approaches often lack single-cell resolution and yield limited read lengths. Here, we introduce spatial ISOform sequencing (Spl-ISO-Seq), which reveals exons and polyadenylation sites with near-single-cell resolution. Spl-ISO-Seq selects long cDNAs and doubles to triples read lengths compared to standard preparations. Adding a highly specific software tool (Spl-ISOquant) and comparing human post-mortem pre-puberty (8-11 years) to post-puberty (16-19 years) visual cortex samples, we find that cortex harbors stronger splicing and poly(A)-site regulation than white matter. However, oligodendrocyte regulation is stronger in white matter. Among cortical layers, layer 4 has the most developmentally-regulated splicing changes in excitatory neurons and in poly(A) sites. We also find repeat elements downstream of developmentally-regulated layer 4 exons. Overall, alternative splicing changes are linked to post-synaptic structure and function. These results root developmental splicing changes during puberty in specific layers and cell types. More generally, our technologies enable exciting observations for any complex tissue.

Indexed as

Alternative SplicingGene Expression Regulation, DevelopmentalPolyadenylationSingle-Cell AnalysisVisual CortexAdolescentChildExonsFemaleHumansMaleNeuronsOligodendrogliaWhite MatterYoung Adult

Identifiers

PMID40883294
PMCPMC12397408

What OpenQuestion 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 OpenQuestion graph.