小柯机器人

单细胞RNA测序揭示肠肌层神经元类别的多样性
2020-12-09 13:22

瑞典卡罗林斯卡医学院Ulrika Marklund研究小组利用单细胞RNA测序揭示肠肌层神经元类别的多样性。相关论文于2020年12月7日在线发表于国际学术期刊《自然—神经科学》。

研究人员使用单细胞RNA测序在小鼠小肠的肠神经丛内定义了12种肠神经元类的分子类别。研究人员报道了运动神经元、感觉神经元和中间神经元的细胞间通讯特征和组织化学标记,以及类别特异性靶向的转基因工具。胚胎肠道神经系统(ENS)的转录组分析揭示了神经元多样化的新原理,其中两种神经元类别通过二元神经原性分支产生,而所以其他的身份通过随后的有丝分裂后分化出现。

研究人员确定了通用和类别特异的转录调节因子,并在功能上将Pbx3与有丝分裂后的命运转换联系起来。这些研究结果为剖析ENS回路和预测关键调节因子提供了概念和分子资源。

据悉,肠道的自主调节需要ENS功能不同的神经元的联合活动。但是,肠神经元类型的多样性以及它们在发育过程中如何出现仍然是未知的。

附:英文原文

Title: Diversification of molecularly defined myenteric neuron classes revealed by single-cell RNA sequencing

Author: Khomgrit Morarach, Anastassia Mikhailova, Viktoria Knoflach, Fatima Memic, Rakesh Kumar, Wei Li, Patrik Ernfors, Ulrika Marklund

Issue&Volume: 2020-12-07

Abstract: Autonomous regulation of the intestine requires the combined activity of functionally distinct neurons of the enteric nervous system (ENS). However, the variety of enteric neuron types and how they emerge during development remain largely unknown. Here, we define a molecular taxonomy of 12 enteric neuron classes within the myenteric plexus of the mouse small intestine using single-cell RNA sequencing. We present cell–cell communication features and histochemical markers for motor neurons, sensory neurons and interneurons, together with transgenic tools for class-specific targeting. Transcriptome analysis of the embryonic ENS uncovers a novel principle of neuronal diversification, where two neuron classes arise through a binary neurogenic branching and all other identities emerge through subsequent postmitotic differentiation. We identify generic and class-specific transcriptional regulators and functionally connect Pbx3 to a postmitotic fate transition. Our results offer a conceptual and molecular resource for dissecting ENS circuits and predicting key regulators for directed differentiation of distinct enteric neuron classes.

DOI: 10.1038/s41593-020-00736-x

Source: https://www.nature.com/articles/s41593-020-00736-x

 

Nature Neuroscience:《自然—神经科学》,创刊于1998年。隶属于施普林格·自然出版集团,最新IF:28.771
官方网址:https://www.nature.com/neuro/
投稿链接:https://mts-nn.nature.com/cgi-bin/main.plex


本期文章:《自然—神经科学》:Online/在线发表

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