title: Comprehensive Classification of Retinal Bipolar Neurons by Single-Cell Transcriptomics.
abstract: Patterns of gene expression can be used to characterize and classify neuronal types. It is challenging, however, to generate taxonomies that fulfill the essential criteria of being comprehensive, harmonizing with conventional classification schemes, and lacking superfluous subdivisions of genuine types. To address these challenges, we used massively parallel single-cell RNA profiling and optimized computational methods on a heterogeneous class of neurons, mouse retinal bipolar cells (BCs). From a population of ∼25,000 BCs, we derived a molecular classification that identified 15 types, including all types observed previously and two novel types, one of which has a non-canonical morphology and position. We validated the classification scheme and identified dozens of novel markers using methods that match molecular expression to cell morphology. This work provides a systematic methodology for achieving comprehensive molecular classification of neurons, identifies novel neuronal types, and uncovers transcriptional differences that distinguish types within a class.
authors: Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
authors: Karthik
authors: K
authors: Shekhar
authors: Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
authors: Sylvain W
authors: SW
authors: Lapan
authors: Center for Brain Science and Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02130, USA.
authors: Irene E
authors: IE
authors: Whitney
authors: Center for Brain Science and Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02130, USA.
authors: Nicholas M
authors: NM
authors: Tran
authors: Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
authors: Evan Z
authors: EZ
authors: Macosko
authors: Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
authors: Monika
authors: M
authors: Kowalczyk
authors: Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
authors: Xian
authors: X
authors: Adiconis
authors: Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
authors: Joshua Z
authors: JZ
authors: Levin
authors: Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
authors: James
authors: J
authors: Nemesh
authors: Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
authors: Melissa
authors: M
authors: Goldman
authors: Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
authors: Steven A
authors: SA
authors: McCarroll
authors: Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Department of Ophthalmology, Harvard Medical School, Boston, MA 02115, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address: cepko@genetics.med.harvard.edu.
authors: Constance L
authors: CL
authors: Cepko
authors: Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; Department of Biology and Koch Institute, MIT, Cambridge, MA 02139, USA. Electronic address: aregev@broadinstitute.org.
authors: Aviv
authors: A
authors: Regev
authors: Center for Brain Science and Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02130, USA. Electronic address: sanesj@mcb.harvard.edu.
authors: Joshua R
authors: JR
authors: Sanes
mesh_terms: D025042:Amacrine Cells / Q000166:cytology; D000818:Animals; D016000:Cluster Analysis; D005260:Female; D005819:Genetic Markers; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D051245:Retinal Bipolar Cells / Q000145:classification* / Q000166:cytology / Q000378:metabolism; D017423:Sequence Analysis, RNA; D059010:Single-Cell Analysis / Q000379:methods; D014158:Transcription, Genetic; D059467:Transcriptome
chemical_list: D005819:Genetic Markers