Journal
SCIENCE
Volume 352, Issue 6293, Pages 1581-1586Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aaf3892
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Funding
- Leona and Harry B. Helmsley Charitable Trust
- Japan Foundation for Applied Enzymology
- Uehara Memorial Foundation
- Alexandre Suerman Stipend
- Royal Netherlands Academy of Sciences
- Prince Bernhard Cultural Foundation
- Deutsche Forschungsgemeinschaft [1410/1]
- Swiss National Science Foundation [0310030-11620]
- National Multiple Sclerosis Society
- Crohn's & Colitis Foundation of America
- Irma T. Hirschl Award
- National Institutes of Health [NIH R01 DK093674]
- Empire State Stem Cell Fund through New York State Department of Health [C023046]
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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.
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