Evidence map›Paper›PMID 40696189›Full record

ArticleNature biotechnology2026

Combined single-cell profiling of chromatin-transcriptome and splicing across brain cell types, regions and disease state.

Wen Hu, Careen Foord, Justine Hsu, Li Fan, Michael J Corley, Samantha N Lanjewar, Siwei Xu, Natan Belchikov, Yi He, Alina P S Pang and 11 more

Abstract read
In one paragraph

Article in Nature biotechnology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing 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

12 citing papers in PubMed.

  1. Article
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  6. cGAS inhibition delays TDP-43-driven ALS Pathogenesis.bioRxiv : the preprint server for biology · 2026
    Article
  7. Review
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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

21 authors.

Wen Hu *Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0002-0604-2119
Careen Foord *Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.
Justine Hsu *Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.
Li FanFeil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.
Michael J CorleyDepartment of Medicine, Division of Infectious Diseases, Weill Cornell Medicine, New York, NY, USA.
Samantha N LanjewarDepartment of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.ORCID http://orcid.org/0000-0002-9227-3668
Siwei XuDepartment of Computer Science, University of California, Irvine, CA, USA.ORCID http://orcid.org/0000-0002-2828-3706
Natan BelchikovFeil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.
Yi HeFeil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.
Alina P S PangDepartment of Medicine, Division of Infectious Diseases, Weill Cornell Medicine, New York, NY, USA.
Tarun N BhatiaDepartment of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.ORCID http://orcid.org/0000-0002-3046-6659
Julien JarrouxFeil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0002-7185-6960
Anoushka JoglekarFeil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0002-7818-6867
Teresa A MilnerFeil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0002-0458-6569
Lishomwa C NdhlovuFeil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0001-5427-4187
Jing ZhangDepartment of Computer Science, University of California, Irvine, CA, USA.
Eduardo ButelmanNeuropsychoimaging of Addiction and Related Conditions Research Program, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0009-0006-9298-7798
Steven A SloanDepartment of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.ORCID http://orcid.org/0000-0001-7769-7684
Virginia M Y LeeCenter for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Li GanFeil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA. lig2033@med.cornell.edu.ORCID http://orcid.org/0000-0003-4600-275X
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

Elucidating single cell changes in neurogenic brain regions during HIV and cannabinoid exposureU01DA058527 · NIDA · WEILL MEDICAL COLL OF CORNELL UNIV · PI Michael Jay Corley, Lishomwa C Ndhlovu · 2023 to 2026
$9.4M
CNS Viral Persistence and Neuropsychiatric Perturbations in HIV: Single cell and Molecular InterrogationR01MH125737 · NIMH · YALE UNIVERSITY · PI CYKTOR, JOSHUA CHARLES, SPUDICH, SERENA S · 2021 to 2025
$5.4M
Impact of IL-15 immunotherapy on tissue-specific CD8 T cells to reduce the CNS HIV reservoir seeding and persistenceR01MH130197 · NIMH · OREGON HEALTH & SCIENCE UNIVERSITY · PI Lishomwa C Ndhlovu, Afamefuna Okoye · 2022 to 2026
$5.1M
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
Decoding epigenetic scars of smoldering neuroinflammation and CNS complications in people with HIVR01MH134391 · NIMH · WEILL MEDICAL COLL OF CORNELL UNIV · PI Michael Jay Corley, Shelli Farhadian · 2023 to 2026
$3.8M
Social epigenetics of Alzheimer's disease and related dementias in Latin American countriesR01AG082056 · NIA · WEILL MEDICAL COLL OF CORNELL UNIV · PI Michael Jay Corley · 2024 to 2026
$3.6M
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
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
Shared mechanisms of astrocyte maturation in development and glioblastomaR01NS123562 · NINDS · EMORY UNIVERSITY · PI SPANGLE, JENNIFER MARIE · 2021 to 2025
$1.9M
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
National Science Foundation (NSF) GRFP # 2139291NIA NIH HHS R01 AG082056NIDA NIH HHS T32 DA039080NIDA NIH HHS U01 DA053625NIDA NIH HHS U01 DA058527NIGMS NIH HHS R01 GM135247NIGMS NIH HHS R35 GM152101NIGMS NIH HHS T32 GM132083NIMH NIH HHS R01 MH125737NIMH NIH HHS R01 MH125956NIMH NIH HHS R01 MH130197NIMH NIH HHS R01 MH134391NIMH NIH HHS RF1 MH121267NINDS NIH HHS R01 NS123562U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) 1R01 GM135247-01U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) 1RF1 MH121267-01U.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 DA053625-01
6 · The paper itself

Abstract

Measuring splicing and chromatin accessibility simultaneously in frozen tissues remains challenging. Here we combined single-cell isoform RNA sequencing and assay for transposase accessible chromatin (ScISOr-ATAC) to interrogate the correlation between these modalities in single cells in human and rhesus macaque frozen cortical tissue samples. Applying a previous definition of four 'cell states' in which the transcriptome and chromatin accessibility are coupled or decoupled for each gene, we demonstrate that splicing patterns in one cell state can differ from those of another state within the same cell type. We also use ScISOr-ATAC to measure the correlation of chromatin and splicing across brain cell types, cortical regions and species (macaque and human) and in Alzheimer's disease. In macaques, some excitatory neuron subtypes show brain-region-specific splicing and chromatin accessibility. In human and macaque prefrontal cortex, strong evolutionary divergence in one molecular modality does not necessarily imply strong divergence in another modality. Finally, in Alzheimer's disease, oligodendrocytes show high dysregulation in both chromatin and splicing.

Indexed as

Alzheimer DiseaseBrainChromatinRNA SplicingSingle-Cell AnalysisTranscriptomeAnimalsGene Expression ProfilingHumansMacaca mulattaNeuronsSingle-Cell Gene Expression AnalysisChromatin

Identifiers

PMID40696189
PMCPMC12425497

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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.