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单细胞RNA测序揭示了通过双潜能中间体形成的感觉神经元的早期多样性。

Single cell RNA sequencing identifies early diversity of sensory neurons forming via bi-potential intermediates.

作者信息

Faure Louis, Wang Yiqiao, Kastriti Maria Eleni, Fontanet Paula, Cheung Kylie K Y, Petitpré Charles, Wu Haohao, Sun Lynn Linyu, Runge Karen, Croci Laura, Landy Mark A, Lai Helen C, Consalez Gian Giacomo, de Chevigny Antoine, Lallemend François, Adameyko Igor, Hadjab Saida

机构信息

Department of Molecular Neurosciences, Center for Brain Research, Medical University Vienna, 1090, Vienna, Austria.

Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.

出版信息

Nat Commun. 2020 Aug 21;11(1):4175. doi: 10.1038/s41467-020-17929-4.

Abstract

Somatic sensation is defined by the existence of a diversity of primary sensory neurons with unique biological features and response profiles to external and internal stimuli. However, there is no coherent picture about how this diversity of cell states is transcriptionally generated. Here, we use deep single cell analysis to resolve fate splits and molecular biasing processes during sensory neurogenesis in mice. Our results identify a complex series of successive and specific transcriptional changes in post-mitotic neurons that delineate hierarchical regulatory states leading to the generation of the main sensory neuron classes. In addition, our analysis identifies previously undetected early gene modules expressed long before fate determination although being clearly associated with defined sensory subtypes. Overall, the early diversity of sensory neurons is generated through successive bi-potential intermediates in which synchronization of relevant gene modules and concurrent repression of competing fate programs precede cell fate stabilization and final commitment.

摘要

躯体感觉是由多种具有独特生物学特征以及对外部和内部刺激有独特反应模式的初级感觉神经元的存在所定义的。然而,关于这种细胞状态的多样性是如何通过转录产生的,目前还没有一个连贯的图景。在这里,我们使用深度单细胞分析来解析小鼠感觉神经发生过程中的命运分歧和分子偏向过程。我们的结果确定了有丝分裂后神经元中一系列复杂的连续和特定转录变化,这些变化描绘了导致主要感觉神经元类别的产生的分层调控状态。此外,我们的分析确定了在命运决定之前很早就表达的、尽管与特定感觉亚型明显相关但以前未被检测到的早期基因模块。总体而言,感觉神经元的早期多样性是通过连续的双潜能中间体产生的,其中相关基因模块的同步化和竞争性命运程序的同时抑制先于细胞命运的稳定和最终决定。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bc6/7442800/66ec8b4b6e52/41467_2020_17929_Fig1_HTML.jpg

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