ArticleMolecular psychiatry2023
Induction of dopaminergic neurons for neuronal subtype-specific modeling of psychiatric disease risk.
Article in Molecular psychiatry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- The Autism-Psychosis Continuum Conundrum: Exploring the Role of the Endocannabinoid System.International journal of environmental research and public health · 2022Pooled it
- Transcriptomic and phenotypic convergence of neurodevelopmental disorder risk genes in vitro and in vivo.Nature neuroscience · 2026Article
- A co-culture model of dopaminergic and glutamatergic neurons derived from patients with idiopathic schizophrenia reveals a hypodopaminergic phenotype.Molecular psychiatry · 2026Article
- Synaptic effects of interleukin-6 on human iPSC-derived dopaminergic neurons.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- 3D genetic architecture of schizophrenia risk across three neuronal subtypes.Molecular psychiatry · 2026Article
- Functional implications of polygenic risk for schizophrenia in human neurons.Nature communications · 2026Article
- Rapid generation of ventral A9-like dopaminergic neurons from patterned iPSCs.bioRxiv : the preprint server for biology · 2025Article
- Dynamic convergence of neurodevelopmental disorder risk genes across neurodevelopment.bioRxiv : the preprint server for biology · 2025Article
- Implications of gene × environment interactions in post-traumatic stress disorder risk and treatment.The Journal of clinical investigation · 2025Review
- Probing the molecular and cellular pathological mechanisms of schizophrenia using human induced pluripotent stem cell models.Schizophrenia research · 2024Review
- Transcription Factor-Mediated Generation of Dopaminergic Neurons from Human iPSCs-A Comparison of Methods.Cells · 2024Article
- Opportunities and limitations for studying neuropsychiatric disorders using patient-derived induced pluripotent stem cells.Molecular psychiatry · 2023Review
- Use ofFrontiers in cellular and infection microbiology · 2023Review
- Review
- Modeling gene × environment interactions in PTSD using human neurons reveals diagnosis-specific glucocorticoid-induced gene expression.Nature neuroscience · 2022Article
- Cannabis Use in Autism: Reasons for Concern about Risk for Psychosis.Healthcare (Basel, Switzerland) · 2022Article
- Mapping cis-regulatory elements in human neurons links psychiatric disease heritability and activity-regulated transcriptional programs.Cell reports · 2022Article
- Making neurons, made easy: The use of Neurogenin-2 in neuronal differentiation.Stem cell reports · 2022Review
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
Dopaminergic neurons are critical to movement, mood, addiction, and stress. Current techniques for generating dopaminergic neurons from human induced pluripotent stem cells (hiPSCs) yield heterogenous cell populations with variable purity and inconsistent reproducibility between donors, hiPSC clones, and experiments. Here, we report the rapid (5 weeks) and efficient (~90%) induction of induced dopaminergic neurons (iDANs) through transient overexpression of lineage-promoting transcription factors combined with stringent selection across five donors. We observe maturation-dependent increase in dopamine synthesis and electrophysiological properties consistent with midbrain dopaminergic neuron identity, such as slow-rising after- hyperpolarization potentials, an action potential duration of ~3 ms, tonic sub-threshold oscillatory activity, and spontaneous burst firing at a frequency of ~1.0-1.75 Hz. Transcriptome analysis reveals robust expression of genes involved in fetal midbrain dopaminergic neuron identity. Specifically expressed genes in iDANs, as well as those from isogenic induced GABAergic and glutamatergic neurons, were enriched in loci conferring heritability for cannabis use disorder, schizophrenia, and bipolar disorder; however, each neuronal subtype demonstrated subtype-specific heritability enrichments in biologically relevant pathways, and iDANs alone were uniquely enriched in autism spectrum disorder risk loci. Therefore, iDANs provide a critical tool for modeling midbrain dopaminergic neuron development and dysfunction in psychiatric disease.
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Registered trials
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.