Department of OMNI Bioinformatics, Genentech, Inc., South San Francisco, CA, USA.
Department of Neuroscience, Genentech, Inc., South San Francisco, CA, USA.
Nat Commun. 2023 Jan 23;14(1):366. doi: 10.1038/s41467-023-36014-0.
Sensory neurons of the dorsal root ganglion (DRG) are critical for maintaining tissue homeostasis by sensing and initiating responses to stimuli. While most preclinical studies of DRGs are conducted in rodents, much less is known about the mechanisms of sensory perception in primates. We generated a transcriptome atlas of mouse, guinea pig, cynomolgus monkey, and human DRGs by implementing a common laboratory workflow and multiple data-integration approaches to generate high-resolution cross-species mappings of sensory neuron subtypes. Using our atlas, we identified conserved core modules highlighting subtype-specific biological processes related to inflammatory response. We also identified divergent expression of key genes involved in DRG function, suggesting species-specific adaptations specifically in nociceptors that likely point to divergent function of nociceptors. Among these, we validated that TAFA4, a member of the druggable genome, was expressed in distinct populations of DRG neurons across species, highlighting species-specific programs that are critical for therapeutic development.
背根神经节(DRG)的感觉神经元通过感知和启动对刺激的反应,对于维持组织内稳态至关重要。虽然大多数 DRG 的临床前研究都是在啮齿动物中进行的,但对于灵长类动物感觉感知的机制知之甚少。我们通过实施常见的实验室工作流程和多种数据集成方法,生成了小鼠、豚鼠、食蟹猴和人 DRG 的转录组图谱,以生成感觉神经元亚型的高分辨率跨物种图谱。使用我们的图谱,我们确定了保守的核心模块,突出了与炎症反应相关的亚型特异性生物学过程。我们还发现了与 DRG 功能相关的关键基因的差异表达,表明特定于 nociceptor 的物种特异性适应,这可能指向 nociceptor 的功能差异。其中,我们验证了 TAFA4,一个可成药基因组的成员,在不同物种的 DRG 神经元中以不同的群体表达,突出了对治疗开发至关重要的物种特异性程序。
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