@article{fc1e9bbdd6044013b34b62a971914d67,
title = "Single-nucleus transcriptome analysis reveals cell-type-specific molecular signatures across reward circuitry in the human brain",
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.",
keywords = "addiction, brain, genomics, neuroscience, psychiatry, reward, single-cell, transcriptomics",
author = "Tran, {Matthew N.} and Maynard, {Kristen R.} and Abby Spangler and Huuki, {Louise A.} and Montgomery, {Kelsey D.} and Vijay Sadashivaiah and Madhavi Tippani and Barry, {Brianna K.} and Hancock, {Dana B.} and Hicks, {Stephanie C.} and Kleinman, {Joel E.} and Hyde, {Thomas M.} and Leonardo Collado-Torres and Jaffe, {Andrew E.} and Keri Martinowich",
note = "Funding Information: The authors would like to express their gratitude to our colleagues, whose efforts have supported the collection of postmortem brain tissue to advance these studies, including at the Office of the Chief Medical Examiner of the State of Maryland, Baltimore. We also would like to acknowledge the contributions of Llewellyn B. Bigelow, MD, and Amy Deep-Soboslay for their diagnostic expertise and Daniel R. Weinberger for providing constructive commentary and editing of the manuscript. Finally, we are indebted to the generosity of the families of the decedents, who donated the brain tissue used in these studies. We thank the Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center (SKCCC) Flow Cytometry Core, especially Jessica Gucwa, and the Johns Hopkins University Transcriptomics and Deep Sequencing Core, especially Linda Orzolek and Haiping Hao, for supporting snRNA-seq data generation. We also thank members of the laboratories of Dr. Weizhe Hong (University of California, Los Angeles) and Dr. Jeremy Day (University of Alabama) for facilitating data sharing and helpful conversations about cross-species comparisons. We also thank Nick Clifton for assisting our group with the initial implementation of MAGMA analyses. Funding for this project was provided by the Lieber Institute for Brain Development . B.K.B., D.B.H., K.M., and A.E.J. were partially supported by R01DA042090 ; K.R.M., A.S., L.C.-T., K.M., and A.E.J. were partially supported by 1R01MH123183 ; and S.C.H. was partially supported by R00HG009007 . Funding Information: The authors would like to express their gratitude to our colleagues, whose efforts have supported the collection of postmortem brain tissue to advance these studies, including at the Office of the Chief Medical Examiner of the State of Maryland, Baltimore. We also would like to acknowledge the contributions of Llewellyn B. Bigelow, MD, and Amy Deep-Soboslay for their diagnostic expertise and Daniel R. Weinberger for providing constructive commentary and editing of the manuscript. Finally, we are indebted to the generosity of the families of the decedents, who donated the brain tissue used in these studies. We thank the Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center (SKCCC) Flow Cytometry Core, especially Jessica Gucwa, and the Johns Hopkins University Transcriptomics and Deep Sequencing Core, especially Linda Orzolek and Haiping Hao, for supporting snRNA-seq data generation. We also thank members of the laboratories of Dr. Weizhe Hong (University of California, Los Angeles) and Dr. Jeremy Day (University of Alabama) for facilitating data sharing and helpful conversations about cross-species comparisons. We also thank Nick Clifton for assisting our group with the initial implementation of MAGMA analyses. Funding for this project was provided by the Lieber Institute for Brain Development. B.K.B. D.B.H. K.M. and A.E.J. were partially supported by R01DA042090; K.R.M. A.S. L.C.-T. K.M. and A.E.J. were partially supported by 1R01MH123183; and S.C.H. was partially supported by R00HG009007. Conceptualization, M.N.T. K.R.M. A.E.J. and K.M.; methodology, M.N.T. K.R.M. B.K.B. S.C.H. T.M.H. L.C.-T. A.E.J. and K.M.; data curation, M.N.T. K.R.M. A.S. K.D.M. and L.C.-T.; validation, K.R.M. and A.S.; investigation, M.N.T. and K.R.M.; formal analysis, M.N.T. L.A.H. V.S. M.T. L.C.-T. and A.E.J.; visualization, M.N.T. K.R.M. A.S. L.A.H. V.S. M.T. B.K.B. L.C.-T. and A.E.J.; resources, J.E.K. and T.M.H.; software, A.E.J.; writing, M.N.T. K.R.M. L.C.-T. A.E.J. and K.M.; project administration, D.B.H. A.E.J. and K.M.; supervision, A.E.J. and K.M.; funding acquisition, D.B.H. A.E.J. and K.M. A.E.J. is employed by a for-profit biotechnology startup company (company name pending), which is unrelated to the content of this manuscript. The remaining authors declare no competing interests. Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",
year = "2021",
month = oct,
day = "6",
doi = "10.1016/j.neuron.2021.09.001",
language = "English (US)",
volume = "109",
pages = "3088--3103.e5",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "19",
}