Variation in Activity State, Axonal Projection, and Position Define the Transcriptional Identity of Individual Neocortical Projection Neurons.

Autor:	Chevée M; Biochemistry, Cellular and Molecular Biology Graduate Program, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA., Robertson JJ; Human Genetics Training Program, McKusick-Nathans Institute for Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA., Cannon GH; McKusick-Nathans Institute for Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA., Brown SP; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: spbrown@jhmi.edu., Goff LA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; McKusick-Nathans Institute for Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: loyalgoff@jhmi.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2018 Jan 09; Vol. 22 (2), pp. 441-455.
DOI:	10.1016/j.celrep.2017.12.046
Abstrakt:	Single-cell RNA sequencing has generated catalogs of transcriptionally defined neuronal subtypes of the brain. However, the cellular processes that contribute to neuronal subtype specification and transcriptional heterogeneity remain unclear. By comparing the gene expression profiles of single layer 6 corticothalamic neurons in somatosensory cortex, we show that transcriptional subtypes primarily reflect axonal projection pattern, laminar position within the cortex, and neuronal activity state. Pseudotemporal ordering of 1,023 cellular responses to sensory manipulation demonstrates that changes in expression of activity-induced genes both reinforced cell-type identity and contributed to increased transcriptional heterogeneity within each cell type. This is due to cell-type biased choices of transcriptional states following manipulation of neuronal activity. These results reveal that axonal projection pattern, laminar position, and activity state define significant axes of variation that contribute both to the transcriptional identity of individual neurons and to the transcriptional heterogeneity within each neuronal subtype. (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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