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A transcriptomic atlas of mouse cerebellar cortex comprehensively defines cell types

The cerebellar cortex is a well-studied brain structure with diverse roles in motor learning, coordination, cognition and autonomic regulation. However,  a complete inventory of cerebellar cell types is currently lacking. Here, using recent advances in high-throughput transcriptional profiling(1–3),...

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Autores principales: Kozareva, Velina, Martin, Caroline, Osorno, Tomas, Rudolph, Stephanie, Guo, Chong, Vanderburg, Charles, Nadaf, Naeem, Regev, Aviv, Regehr, Wade G., Macosko, Evan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494635/
https://www.ncbi.nlm.nih.gov/pubmed/34616064
http://dx.doi.org/10.1038/s41586-021-03220-z
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author Kozareva, Velina
Martin, Caroline
Osorno, Tomas
Rudolph, Stephanie
Guo, Chong
Vanderburg, Charles
Nadaf, Naeem
Regev, Aviv
Regehr, Wade G.
Macosko, Evan
author_facet Kozareva, Velina
Martin, Caroline
Osorno, Tomas
Rudolph, Stephanie
Guo, Chong
Vanderburg, Charles
Nadaf, Naeem
Regev, Aviv
Regehr, Wade G.
Macosko, Evan
author_sort Kozareva, Velina
collection PubMed
description The cerebellar cortex is a well-studied brain structure with diverse roles in motor learning, coordination, cognition and autonomic regulation. However,  a complete inventory of cerebellar cell types is currently lacking. Here, using recent advances in high-throughput transcriptional profiling(1–3), we molecularly define cell types across individual lobules of the adult mouse cerebellum. Purkinje neurons showed considerable regional specialization, with the greatest diversity occurring in the posterior lobules. For several types of cerebellar interneuron, the molecular variation within each type was more continuous, rather than discrete. In particular, for the unipolar brush cells—an interneuron population previously subdivided into discrete populations—the continuous variation in gene expression was associated with a graded continuum of electrophysiological properties. Notably, we found that molecular layer interneurons were composed of two molecularly and functionally distinct types. Both types show a continuum of morphological variation through the thickness of the molecular layer, but electrophysiological recordings revealed marked differences between the two types in spontaneous firing, excitability and electrical coupling. Together, these findings provide a comprehensive cellular atlas of the cerebellar cortex, and outline a methodological and conceptual framework for the integration of molecular, morphological and physiological ontologies for defining brain cell types.
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spelling pubmed-84946352021-10-19 A transcriptomic atlas of mouse cerebellar cortex comprehensively defines cell types Kozareva, Velina Martin, Caroline Osorno, Tomas Rudolph, Stephanie Guo, Chong Vanderburg, Charles Nadaf, Naeem Regev, Aviv Regehr, Wade G. Macosko, Evan Nature Article The cerebellar cortex is a well-studied brain structure with diverse roles in motor learning, coordination, cognition and autonomic regulation. However,  a complete inventory of cerebellar cell types is currently lacking. Here, using recent advances in high-throughput transcriptional profiling(1–3), we molecularly define cell types across individual lobules of the adult mouse cerebellum. Purkinje neurons showed considerable regional specialization, with the greatest diversity occurring in the posterior lobules. For several types of cerebellar interneuron, the molecular variation within each type was more continuous, rather than discrete. In particular, for the unipolar brush cells—an interneuron population previously subdivided into discrete populations—the continuous variation in gene expression was associated with a graded continuum of electrophysiological properties. Notably, we found that molecular layer interneurons were composed of two molecularly and functionally distinct types. Both types show a continuum of morphological variation through the thickness of the molecular layer, but electrophysiological recordings revealed marked differences between the two types in spontaneous firing, excitability and electrical coupling. Together, these findings provide a comprehensive cellular atlas of the cerebellar cortex, and outline a methodological and conceptual framework for the integration of molecular, morphological and physiological ontologies for defining brain cell types. Nature Publishing Group UK 2021-10-06 2021 /pmc/articles/PMC8494635/ /pubmed/34616064 http://dx.doi.org/10.1038/s41586-021-03220-z Text en © The Author(s) 2021, corrected publication 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Kozareva, Velina
Martin, Caroline
Osorno, Tomas
Rudolph, Stephanie
Guo, Chong
Vanderburg, Charles
Nadaf, Naeem
Regev, Aviv
Regehr, Wade G.
Macosko, Evan
A transcriptomic atlas of mouse cerebellar cortex comprehensively defines cell types
title A transcriptomic atlas of mouse cerebellar cortex comprehensively defines cell types
title_full A transcriptomic atlas of mouse cerebellar cortex comprehensively defines cell types
title_fullStr A transcriptomic atlas of mouse cerebellar cortex comprehensively defines cell types
title_full_unstemmed A transcriptomic atlas of mouse cerebellar cortex comprehensively defines cell types
title_short A transcriptomic atlas of mouse cerebellar cortex comprehensively defines cell types
title_sort transcriptomic atlas of mouse cerebellar cortex comprehensively defines cell types
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494635/
https://www.ncbi.nlm.nih.gov/pubmed/34616064
http://dx.doi.org/10.1038/s41586-021-03220-z
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