研究揭示小鼠運動皮層轉錄組細胞類型的表型變異
作者：
小柯機器人發布時間：2020/11/16 13:56:35
美國貝勒醫學院Andreas S. Tolias、德國圖賓根大學Philipp Berens等研究人員合作揭示小鼠運動皮層轉錄組細胞類型的表型變異。相關論文於2020年11月12日在線發表於國際學術期刊《自然》。
研究人員使用Patch-seq並結合膜片鉗記錄、生物胞素染色和成年小鼠原代運動皮層中1,300多個神經元的單細胞RNA測序，來提供了幾乎所有轉錄組定義神經細胞類型的形-電注釋。研究人員發現，儘管轉錄組類型的廣泛家族（表達Vip、Pvalb，Sst等的家族）具有截然不同且基本不重疊的形-電錶型，但同一家族中的各個轉錄組類型在形-電空間中並未很好地分離。取而代之的是，形態和電生理學具有連續性的變化，相鄰的轉錄組細胞類型顯示出相似的形-電特徵，它們之間通常沒有明確的界限。
這些結果表明，新皮層中的神經元類型並不總是形成離散實體。取而代之的是，神經元形成了一個層次結構，該層次結構由家族級別的不同的非重疊分支組成，但可以在家族內部形成連續且相關的轉錄組和形-電圖譜。
據介紹，皮質神經元在基因表達以及形態和電生理特性上表現出極大的多樣性。大多數現有的神經分類法都基於轉錄組或電生理性質，因為在同一組細胞中研究神經元多樣性的兩個方面在技術上都具有挑戰性。
附：英文原文
Title: Phenotypic variation of transcriptomic cell types in mouse motor cortex
Author: Federico Scala, Dmitry Kobak, Matteo Bernabucci, Yves Bernaerts, Cathryn Ren Cadwell, Jesus Ramon Castro, Leonard Hartmanis, Xiaolong Jiang, Sophie Laturnus, Elanine Miranda, Shalaka Mulherkar, Zheng Huan Tan, Zizhen Yao, Hongkui Zeng, Rickard Sandberg, Philipp Berens, Andreas S. Tolias
Issue&Volume: 2020-11-12
Abstract: Cortical neurons exhibit extreme diversity in gene expression as well as in morphological and electrophysiological properties1,2. Most existing neural taxonomies are based on either transcriptomic3,4 or morpho-electric5,6 criteria, as it has been technically challenging to study both aspects of neuronal diversity in the same set of cells7. Here we used Patch-seq8 to combine patch-clamp recording, biocytin staining, and single-cell RNA sequencing of more than 1,300 neurons in adult mouse primary motor cortex, providing a morpho-electric annotation of almost all transcriptomically defined neural cell types. We found that, although broad families of transcriptomic types (those expressing Vip, Pvalb, Sst and so on) had distinct and essentially non-overlapping morpho-electric phenotypes, individual transcriptomic types within the same family were not well separated in the morpho-electric space. Instead, there was a continuum of variability in morphology and electrophysiology, with neighbouring transcriptomic cell types showing similar morpho-electric features, often without clear boundaries between them. Our results suggest that neuronal types in the neocortex do not always form discrete entities. Instead, neurons form a hierarchy that consists of distinct non-overlapping branches at the level of families, but can form continuous and correlated transcriptomic and morpho-electrical landscapes within families. Single-cell transcriptomic, morphological and electrophysiological characteristics are combined to classify more than 1,300 neurons from mouse motor cortex.
DOI: 10.1038/s41586-020-2907-3
Source: https://www.nature.com/articles/s41586-020-2907-3