title: Neuronal subtypes and diversity revealed by single-nucleus RNA sequencing of the human brain.
abstract: The human brain has enormously complex cellular diversity and connectivities fundamental to our neural functions, yet difficulties in interrogating individual neurons has impeded understanding of the underlying transcriptional landscape. We developed a scalable approach to sequence and quantify RNA molecules in isolated neuronal nuclei from a postmortem brain, generating 3227 sets of single-neuron data from six distinct regions of the cerebral cortex. Using an iterative clustering and classification approach, we identified 16 neuronal subtypes that were further annotated on the basis of known markers and cortical cytoarchitecture. These data demonstrate a robust and scalable method for identifying and categorizing single nuclear transcriptomes, revealing shared genes sufficient to distinguish previously unknown and orthologous neuronal subtypes as well as regional identity and transcriptomic heterogeneity within the human brain.
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Blue B
authors.initials: BB
authors.lastname: Lake
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Rizi
authors.initials: R
authors.lastname: Ai
authors.affiliation: Department of Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA, USA. Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Gwendolyn E
authors.initials: GE
authors.lastname: Kaeser
authors.affiliation: Illumina, San Diego, CA, USA.
authors.forename: Neeraj S
authors.initials: NS
authors.lastname: Salathia
authors.affiliation: Department of Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Yun C
authors.initials: YC
authors.lastname: Yung
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Andre
authors.initials: A
authors.lastname: Wildberg
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Derek
authors.initials: D
authors.lastname: Gao
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Ho-Lim
authors.initials: HL
authors.lastname: Fung
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Song
authors.initials: S
authors.lastname: Chen
authors.affiliation: Illumina, San Diego, CA, USA.
authors.forename: Raakhee
authors.initials: R
authors.lastname: Vijayaraghavan
authors.affiliation: Department of Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Julian
authors.initials: J
authors.lastname: Wong
authors.affiliation: Department of Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Allison
authors.initials: A
authors.lastname: Chen
authors.affiliation: Department of Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Sheng
authors.affiliation: Illumina, San Diego, CA, USA.
authors.forename: Fiona
authors.initials: F
authors.lastname: Kaper
authors.affiliation: Illumina, San Diego, CA, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Shen
authors.affiliation: Illumina, San Diego, CA, USA.
authors.forename: Mostafa
authors.initials: M
authors.lastname: Ronaghi
authors.affiliation: Illumina, San Diego, CA, USA. kzhang@bioeng.ucsd.edu jchun@scripps.edu wei-wang@ucsd.edu jianbing_fan@yahoo.com.
authors.forename: Jian-Bing
authors.initials: JB
authors.lastname: Fan
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, USA. kzhang@bioeng.ucsd.edu jchun@scripps.edu wei-wang@ucsd.edu jianbing_fan@yahoo.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA, USA. kzhang@bioeng.ucsd.edu jchun@scripps.edu wei-wang@ucsd.edu jianbing_fan@yahoo.com.
authors.forename: Jerold
authors.initials: J
authors.lastname: Chun
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA. kzhang@bioeng.ucsd.edu jchun@scripps.edu wei-wang@ucsd.edu jianbing_fan@yahoo.com.
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
mesh_terms: D002467:Cell Nucleus; D002540:Cerebral Cortex; D020869:Gene Expression Profiling; D006801:Humans; D009474:Neurons; D017423:Sequence Analysis, RNA; D059467:Transcriptome