Cited by 219Single-cell and spatial transcriptomicsNeurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology Research

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Single-nucleus transcriptome analysis reveals cell-type-specific molecular signatures across reward circuitry in the human brain

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Tran, Matthew N., Maynard, Kristen R., Spangler, Abby, Huuki, Louise A., Montgomery, Kelsey D., Sadashivaiah, Vijay, Tippani, Madhavi, Barry, Brianna K., Hancock, Dana B., Hicks, Stephanie C., Kleinman, Joel E., Hyde, Thomas M., Collado-Torres, Leonardo, Jaffe, Andrew E., Martinowich, Keri·2021·Neuron

DOI 10.1016/j.neuron.2021.09.001PMC PMC8564763

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Abstract

Single-cell gene expression technologies are powerful tools to study cell types in the human brain, but efforts have largely focused on cortical brain regions. We therefore created a single-nucleus RNA-sequencing resource of 70,615 high-quality nuclei to generate a molecular taxonomy of cell types across five human brain regions that serve as key nodes of the human brain reward circuitry: nucleus accumbens, amygdala, subgenual anterior cingulate cortex, hippocampus, and dorsolateral prefrontal cortex. We first identified novel subpopulations of interneurons and medium spiny neurons (MSNs) in the nucleus accumbens and further characterized robust GABAergic inhibitory cell populations in the amygdala. Joint analyses across the 107 reported cell classes revealed cell-type substructure and unique patterns of transcriptomic dynamics. We identified discrete subpopulations of D1- and D2-expressing MSNs in the nucleus accumbens to which we mapped cell-type-specific enrichment for genetic risk associated with both psychiatric disease and addiction.

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Authors: Tran, M. N., Maynard, K. R., Spangler, A., Huuki, L. A., Montgomery, K. D., Sadashivaiah, V., Tippani, M., Barry, B. K., Hancock, D. B., Hicks, S. C., Kleinman, J. E., Hyde, T. M., Collado-Torres, L., Jaffe, A. E., & Martinowich, K.
Affiliations: Johns Hopkins University (US)
RTI International (US)
Corresponding author: Jaffe, Andrew E.
Martinowich, Keri
ORCID: Tran, Matthew N.
Maynard, Kristen R.
Spangler, Abby
Huuki, Louise A.
Montgomery, Kelsey D.
Sadashivaiah, Vijay
Tippani, Madhavi
Barry, Brianna K.
Hancock, Dana B.
Hicks, Stephanie C.
Kleinman, Joel E.
Hyde, Thomas M.
Collado-Torres, Leonardo
Jaffe, Andrew E.
Martinowich, Keri
Venue: Neuron
Publisher: Elsevier BV
Published: 2021-10
Volume: 109
Issue: 19
Pages: 3088-3103.e5
ISSN: 0896-6273 (ISSN-L)
DOI: 10.1016/j.neuron.2021.09.001
PMC: PMC8564763
OpenAlex: W3203631316
Cited by: 219
References: 116
Citations by year: 2026: 34 · 2025: 42 · 2024: 61 · 2023: 53 · 2022: 25 · 2021: 4
FWCI: 11.22
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 370 d)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Neuron (publishedVersion)
bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: NHGRI (R00HG009007)
Lieber Institute for Brain Development (1R01MH123183)
National Institute of Mental Health
National Institute on Drug Abuse (R01DA042090)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: single-nucleus transcriptomics, nucleus accumbens, amygdala, subgenual anterior cingulate cortex, hippocampus, dorsolateral prefrontal cortex, interneurons, medium spiny neurons, cell type-specific gene expression
MeSH terms: Mental Disorders, Brain, Brain Mapping, Cell Nucleus, gamma-Aminobutyric Acid, Humans, Interneurons, Nerve Net, Neurons, Reward, Sequence Analysis, RNA, Substance-Related Disorders, Gene Expression Profiling, Genome-Wide Association Study, High-Throughput Nucleotide Sequencing

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Single-nucleus transcriptome analysis reveals cell-type-specific molecular signatures across reward circuitry in the human brain

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