Department of Neuroscience, Division of Biology and Medicine, and the Robert J. and Nancy D. Carney Institute for Brain Science, Brown University, Providence, United States; Center for Interdisciplinary Research in Biology (CIRB), Collège de France, and CNRS UMR 7241 and INSERM U1050, Paris, France
The Francis Crick Institute, Sensory Circuits and Neurotechnology Laboratory, London, United Kingdom; Department of Neuroscience, Physiology & Pharmacology, University College London, London, United Kingdom
Department of Neuroscience, Division of Biology and Medicine, and the Robert J. and Nancy D. Carney Institute for Brain Science, Brown University, Providence, United States
Department of Neuroscience, Division of Biology and Medicine, and the Robert J. and Nancy D. Carney Institute for Brain Science, Brown University, Providence, United States
The Francis Crick Institute, Bioinformatics and Biostatistics, London, United Kingdom; The Francis Crick Institute, Scientific Computing - Digital Development Team, London, United Kingdom
The Francis Crick Institute, Sensory Circuits and Neurotechnology Laboratory, London, United Kingdom; Department of Neuroscience, Physiology & Pharmacology, University College London, London, United Kingdom
Department of Neuroscience, Division of Biology and Medicine, and the Robert J. and Nancy D. Carney Institute for Brain Science, Brown University, Providence, United States; Center for Interdisciplinary Research in Biology (CIRB), Collège de France, and CNRS UMR 7241 and INSERM U1050, Paris, France
Projection neurons (PNs) in the mammalian olfactory bulb (OB) receive input from the nose and project to diverse cortical and subcortical areas. Morphological and physiological studies have highlighted functional heterogeneity, yet no molecular markers have been described that delineate PN subtypes. Here, we used viral injections into olfactory cortex and fluorescent nucleus sorting to enrich PNs for high-throughput single nucleus and bulk RNA deep sequencing. Transcriptome analysis and RNA in situ hybridization identified distinct mitral and tufted cell populations with characteristic transcription factor network topology, cell adhesion, and excitability-related gene expression. Finally, we describe a new computational approach for integrating bulk and snRNA-seq data and provide evidence that different mitral cell populations preferentially project to different target regions. Together, we have identified potential molecular and gene regulatory mechanisms underlying PN diversity and provide new molecular entry points into studying the diverse functional roles of mitral and tufted cell subtypes.
