美国哈佛医学院神经生物学系David D. Ginty研究团队研究揭示体感神经元转录出现同一性。相关论文2020年1月8日在线发表于国际学术期刊《自然》上。
为了评估主要体感神经元的每个亚型的转录成熟的发育进程，他们绘制小鼠中初级体感神经元谱系的细胞转录组图谱。体感神经发生以转录非特化状态产生神经元，其特征是随着发育的进行，转录因子的共表达受限于选择的亚型。来自缺乏转录因子的突变小鼠的感觉神经元的单细胞转录组学分析表明，这些从广泛到限制的转录因子在维持其表达的亚型中协调亚型特异性基因表达程序。他们还表明，神经元靶标参与了这个过程。原型靶标来源的神经营养因子NGF的破坏会导致转录因子表达的异常亚型限制模式。他们的发现支持一种模型，在该模型中，从中间目标域和最终目标域发出的信号通过调节亚型限制性转录因子的选择，将细胞从转录非化状态转变为转录上的不同亚型，从而部分促进了神经元的多样化。
据悉，超过十二种初级体感神经元的形态和生理上不同的亚型揭示了人体内部和外部环境的显著特征。在发育过程中如何出现特化基因表达程序来赋予这些亚型独特特性尚不清楚。
附：英文原文
Title: The emergence of transcriptional identity in somatosensory neurons
Author: Nikhil Sharma, Kali Flaherty, Karina Lezgiyeva, Daniel E. Wagner, Allon M. Klein, David D. Ginty
Issue&Volume: 2020-01-08
Abstract: More than twelve morphologically and physiologically distinct subtypes of primary somatosensory neuron report salient features of our internal and external environments14. It is unclear how specialized gene expression programs emerge during development to endow these subtypes with their unique properties. To assess the developmental progression of transcriptional maturation of each subtype of principal somatosensory neuron, we generated a transcriptomic atlas of cells traversing the primary somatosensory neuron lineage in mice. Here we show that somatosensory neurogenesis gives rise to neurons in a transcriptionally unspecialized state, characterized by co-expression of transcription factors that become restricted to select subtypes as development proceeds. Single-cell transcriptomic analyses of sensory neurons from mutant mice lacking transcription factors suggest that these broad-to-restricted transcription factors coordinate subtype-specific gene expression programs in subtypes in which their expression is maintained. We also show that neuronal targets are involved in this process; disruption of the prototypic target-derived neurotrophic factor NGF leads to aberrant subtype-restricted patterns of transcription factor expression. Our findings support a model in which cues that emanate from intermediate and final target fields promote neuronal diversification in part by transitioning cells from a transcriptionally unspecialized state to transcriptionally distinct subtypes by modulating the selection of subtype-restricted transcription factors. Neuronal targets mediate the emergence of somatosensory neuron subtypes by altering the expression of neuronal transcription factors.
DOI: 10.1038/s41586-019-1900-1
Source:https://www.nature.com/articles/s41586-019-1900-1
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
