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Single-cell transcriptomics of the developing lateral geniculate nucleus reveals insights into circuit assembly and refinement

Coordinated changes in gene expression underlie the early patterning and cell-type specification of the central nervous system. However, much less is known about how such changes contribute to later stages of circuit assembly and refinement. In this study, we employ single-cell RNA sequencing to dev...

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Autores principales: Kalish, Brian T., Cheadle, Lucas, Hrvatin, Sinisa, Nagy, M. Aurel, Rivera, Samuel, Crow, Megan, Gillis, Jesse, Kirchner, Rory, Greenberg, Michael E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5798372/
https://www.ncbi.nlm.nih.gov/pubmed/29343640
http://dx.doi.org/10.1073/pnas.1717871115
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author Kalish, Brian T.
Cheadle, Lucas
Hrvatin, Sinisa
Nagy, M. Aurel
Rivera, Samuel
Crow, Megan
Gillis, Jesse
Kirchner, Rory
Greenberg, Michael E.
author_facet Kalish, Brian T.
Cheadle, Lucas
Hrvatin, Sinisa
Nagy, M. Aurel
Rivera, Samuel
Crow, Megan
Gillis, Jesse
Kirchner, Rory
Greenberg, Michael E.
author_sort Kalish, Brian T.
collection PubMed
description Coordinated changes in gene expression underlie the early patterning and cell-type specification of the central nervous system. However, much less is known about how such changes contribute to later stages of circuit assembly and refinement. In this study, we employ single-cell RNA sequencing to develop a detailed, whole-transcriptome resource of gene expression across four time points in the developing dorsal lateral geniculate nucleus (LGN), a visual structure in the brain that undergoes a well-characterized program of postnatal circuit development. This approach identifies markers defining the major LGN cell types, including excitatory relay neurons, oligodendrocytes, astrocytes, microglia, and endothelial cells. Most cell types exhibit significant transcriptional changes across development, dynamically expressing genes involved in distinct processes including retinotopic mapping, synaptogenesis, myelination, and synaptic refinement. Our data suggest that genes associated with synapse and circuit development are expressed in a larger proportion of nonneuronal cell types than previously appreciated. Furthermore, we used this single-cell expression atlas to identify the Prkcd-Cre mouse line as a tool for selective manipulation of relay neurons during a late stage of sensory-driven synaptic refinement. This transcriptomic resource provides a cellular map of gene expression across several cell types of the LGN, and offers insight into the molecular mechanisms of circuit development in the postnatal brain.
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spelling pubmed-57983722018-02-06 Single-cell transcriptomics of the developing lateral geniculate nucleus reveals insights into circuit assembly and refinement Kalish, Brian T. Cheadle, Lucas Hrvatin, Sinisa Nagy, M. Aurel Rivera, Samuel Crow, Megan Gillis, Jesse Kirchner, Rory Greenberg, Michael E. Proc Natl Acad Sci U S A PNAS Plus Coordinated changes in gene expression underlie the early patterning and cell-type specification of the central nervous system. However, much less is known about how such changes contribute to later stages of circuit assembly and refinement. In this study, we employ single-cell RNA sequencing to develop a detailed, whole-transcriptome resource of gene expression across four time points in the developing dorsal lateral geniculate nucleus (LGN), a visual structure in the brain that undergoes a well-characterized program of postnatal circuit development. This approach identifies markers defining the major LGN cell types, including excitatory relay neurons, oligodendrocytes, astrocytes, microglia, and endothelial cells. Most cell types exhibit significant transcriptional changes across development, dynamically expressing genes involved in distinct processes including retinotopic mapping, synaptogenesis, myelination, and synaptic refinement. Our data suggest that genes associated with synapse and circuit development are expressed in a larger proportion of nonneuronal cell types than previously appreciated. Furthermore, we used this single-cell expression atlas to identify the Prkcd-Cre mouse line as a tool for selective manipulation of relay neurons during a late stage of sensory-driven synaptic refinement. This transcriptomic resource provides a cellular map of gene expression across several cell types of the LGN, and offers insight into the molecular mechanisms of circuit development in the postnatal brain. National Academy of Sciences 2018-01-30 2018-01-17 /pmc/articles/PMC5798372/ /pubmed/29343640 http://dx.doi.org/10.1073/pnas.1717871115 Text en Copyright © 2018 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/ This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle PNAS Plus
Kalish, Brian T.
Cheadle, Lucas
Hrvatin, Sinisa
Nagy, M. Aurel
Rivera, Samuel
Crow, Megan
Gillis, Jesse
Kirchner, Rory
Greenberg, Michael E.
Single-cell transcriptomics of the developing lateral geniculate nucleus reveals insights into circuit assembly and refinement
title Single-cell transcriptomics of the developing lateral geniculate nucleus reveals insights into circuit assembly and refinement
title_full Single-cell transcriptomics of the developing lateral geniculate nucleus reveals insights into circuit assembly and refinement
title_fullStr Single-cell transcriptomics of the developing lateral geniculate nucleus reveals insights into circuit assembly and refinement
title_full_unstemmed Single-cell transcriptomics of the developing lateral geniculate nucleus reveals insights into circuit assembly and refinement
title_short Single-cell transcriptomics of the developing lateral geniculate nucleus reveals insights into circuit assembly and refinement
title_sort single-cell transcriptomics of the developing lateral geniculate nucleus reveals insights into circuit assembly and refinement
topic PNAS Plus
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5798372/
https://www.ncbi.nlm.nih.gov/pubmed/29343640
http://dx.doi.org/10.1073/pnas.1717871115
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