Evidence map›Paper›PMID 36302966›Full record

ArticleMolecular psychiatry2024

Single cell transcriptomics reveals distinct transcriptional responses to oxycodone and buprenorphine by iPSC-derived brain organoids from patients with opioid use disorder.

Ming-Fen Ho, Cheng Zhang, Irene Moon, Xiujuan Zhu, Brandon J Coombes, Joanna Biernacka, Michelle Skime, Tyler S Oesterle, Victor M Karpyak, Kristen Schmidt and 6 more

Open access · hybridAbstract read
In one paragraph

Article in Molecular psychiatry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 1 pooled it
2.4field-weighted citation impact, top 10% 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

28 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.

  1. Pooled it
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  7. Review
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  17. A Comprehensive Review on Utilizing Human Brain Organoids to Study Neuroinflammation in Neurological Disorders.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025
    Review
  18. Review
  19. Article
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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

16 authors at 3 institutions in 1 country.

Ming-Fen HoDepartment of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA. ho.mingfen@mayo.edu.ORCID 0000-0002-3757-3924
Cheng ZhangDepartment of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.
Irene MoonDepartment of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.
Xiujuan ZhuDepartment of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.
Brandon J CoombesDivision of Computational Biology, Quantitative Health Sciences; Mayo Clinic, Rochester, MN, USA.ORCID 0000-0003-4322-5923
Joanna BiernackaDivision of Computational Biology, Quantitative Health Sciences; Mayo Clinic, Rochester, MN, USA.ORCID 0000-0001-9350-4440
Michelle SkimeDepartment of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0001-7863-3017
Tyler S OesterleDepartment of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0002-7363-8086
Victor M KarpyakDepartment of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0002-9552-6130
Kristen SchmidtHazelden Betty Ford Foundation, Center City, Minnesota, USA.
Kate GliskeHazelden Betty Ford Foundation, Center City, Minnesota, USA.
Quyen NgoHazelden Betty Ford Foundation, Center City, Minnesota, USA.
Cedric SkillonHazelden Betty Ford Foundation, Center City, Minnesota, USA.
Marvin D SeppalaHazelden Betty Ford Foundation, Center City, Minnesota, USA.
Hu LiDepartment of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0001-5957-5472
Richard M WeinshilboumDepartment of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA. weinshilboum.richard@mayo.edu.ORCID 0000-0002-4911-7985
Mayo Clinic · USFord Foundation · USQuantitative BioSciences · US

Funding

Alcohol Use Disorder: Acamprosate Pharmacometabolomics-informed PharmacogenomicsR01AA027486 · NIAAA · MAYO CLINIC ROCHESTER · PI Ming-Fen Ho, Richard M. Weinshilboum · 2018 to 2026
$4.0M
Peripheral Nerve Function Decline in an Aged CohortR01AG028050 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI STROTMEYER, ELSA S. · 2007 to 2015
$3.5M
Single cell multi-omics of iPSC-derived brain organoids from patients with opioid use disorder: synthetic opioids as molecular probesR01DA057928 · NIDA · MAYO CLINIC ROCHESTER · PI Ming-Fen Ho · 2023 to 2026
$1.7M
Acamprosate pharmacogenomics: iPSC based model of alcohol use disorderK01AA028050 · NIAAA · MAYO CLINIC ROCHESTER · PI HO, MING-FEN · 2019 to 2024
$649k
NIAAA NIH HHS K01 AA028050NIAAA NIH HHS R01 AA027486NIDA NIH HHS R01 DA057928U.S. Department of Health & Human Services | NIH | National Institute on Alcohol Abuse and Alcoholism (NIAAA) AA27486U.S. Department of Health & Human Services | NIH | National Institute on Alcohol Abuse and Alcoholism (NIAAA) AA28050
6 · The paper itself

Abstract

The opioid epidemic represents a national crisis. Oxycodone is one of the most prescribed opioid medications in the United States, whereas buprenorphine is currently the most prescribed medication for opioid use disorder (OUD) pharmacotherapy. Given the extensive use of prescription opioids and the global opioid epidemic, it is essential to understand how opioids modulate brain cell type function at the single-cell level. We performed single nucleus RNA-seq (snRNA-seq) using iPSC-derived forebrain organoids from three male OUD subjects in response to oxycodone, buprenorphine, or vehicle for seven days. We utilized the snRNA-seq data to identify differentially expressed genes following drug treatment using the Seurat integrative analysis pipeline. We utilized iPSC-derived forebrain organoids and single-cell sequencing technology as an unbiased tool to study cell-type-specific and drug-specific transcriptional responses. After quality control filtering, we analyzed 25787 cells and identified sixteen clusters using unsupervised clustering analysis. Our results reveal distinct transcriptional responses to oxycodone and buprenorphine by iPSC-derived brain organoids from patients with OUD. Specifically, buprenorphine displayed a significant influence on transcription regulation in glial cells. However, oxycodone induced type I interferon signaling in many cell types, including neural cells in brain organoids. Finally, we demonstrate that oxycodone, but not buprenorphine activated STAT1 and induced the type I interferon signaling in patients with OUD. These data suggest that elevation of STAT1 expression associated with OUD might play a role in transcriptional regulation in response to oxycodone. In summary, our results provide novel mechanistic insight into drug action at single-cell resolution.

Indexed as

Analgesics, OpioidBrainBuprenorphineInduced Pluripotent Stem CellsOpioid-Related DisordersOrganoidsOxycodoneSingle-Cell AnalysisTranscriptomeHumansMaleProsencephalonAnalgesics, OpioidBuprenorphineOxycodone

Identifiers

PMID36302966
PMCPMC10588459
OpenAlexW4307501132

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.