Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Department of Anesthesia, Critical Care, and Pain Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA.
Neuron. 2022 Jun 1;110(11):1806-1821.e8. doi: 10.1016/j.neuron.2022.03.003. Epub 2022 Mar 28.
Sensitization of trigeminal ganglion neurons contributes to primary headache disorders such as migraine, but the specific neuronal and non-neuronal trigeminal subtypes that are involved remain unclear. We thus developed a cell atlas in which human and mouse trigeminal ganglia are transcriptionally and epigenomically profiled at single-cell resolution. These data describe evolutionarily conserved and human-specific gene expression patterns within each trigeminal ganglion cell type, as well as the transcription factors and gene regulatory elements that contribute to cell-type-specific gene expression. We then leveraged these data to identify trigeminal ganglion cell types that are implicated both by human genetic variation associated with migraine and two mouse models of headache. This trigeminal ganglion cell atlas improves our understanding of the cell types, genes, and epigenomic features involved in headache pathophysiology and establishes a rich resource of cell-type-specific molecular features to guide the development of more selective treatments for headache and facial pain.
三叉神经节神经元的致敏作用导致原发性头痛疾病，如偏头痛，但涉及的具体三叉神经亚型和非神经元仍不清楚。因此，我们开发了一个细胞图谱，以单细胞分辨率对人和小鼠三叉神经节进行转录组和表观基因组分析。这些数据描述了每个三叉神经节细胞类型内进化保守和人类特有的基因表达模式，以及有助于细胞类型特异性基因表达的转录因子和基因调控元件。然后，我们利用这些数据来鉴定与偏头痛相关的人类遗传变异和两种头痛小鼠模型都涉及的三叉神经节细胞类型。这个三叉神经节细胞图谱提高了我们对涉及头痛病理生理学的细胞类型、基因和表观基因组特征的理解，并建立了一个丰富的细胞类型特异性分子特征资源，以指导针对头痛和面部疼痛的更具选择性的治疗方法的开发。
