A transcriptomic atlas of mouse cerebellar cortex comprehensively defines cell types.

A transcriptomic atlas of mouse cerebellar cortex comprehensively defines cell types.
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小鼠小脑皮层的转录组图谱全面定义了细胞类型。

DOI:
10.1038/s41586-021-03220-z
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发表时间:
2021-10
期刊:
影响因子:
64.8
通讯作者:
Macosko E
Macosko E
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Kozareva V;Martin C;Osorno T;Rudolph S;Guo C;Vanderburg C;Nadaf N;Regev A;Regehr WG;Macosko E

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小脑皮层在运动学习、协调、认知和自主调节等方面发挥着多种作用。然而,目前缺乏小脑细胞类型的完整清单。在这里,利用高通量转录谱的最新进展,我们从分子上定义了成年小鼠小脑单个小叶的细胞类型。浦肯野神经元表现出相当大的区域特化,最大的多样性发生在后小叶。对于几种类型的小脑中间神经元,每种类型的分子变异都是连续的,而不是离散的。特别是,对于单极刷状细胞——一种之前被细分为离散群体的中间神经元群体——基因表达的连续变化与电生理特性的梯度连续相关联。值得注意的是,我们发现分子层中间神经元由两种分子和功能不同的类型组成。这两种类型在分子层厚度上都表现出连续的形态变化,但电生理记录显示两种类型在自发放电、兴奋性和电耦合方面存在显著差异。总之,这些发现提供了小脑皮层的全面细胞图谱,并概述了用于定义脑细胞类型的分子、形态和生理本体论整合的方法和概念框架。小鼠小脑皮层细胞类型和区域特化的综合图谱。
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, 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. A comprehensive atlas of cell types and regional specializations in the mouse cerebellar cortex.
DOI: 10.1038/s41586-019-0969-x
发表时间: 2019-02-28
期刊: NATURE
影响因子: 64.8
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