Spatial transcriptomics (ST) is a cutting-edge methodology that enables the simultaneous profiling of global gene expression and spatial information within histological tissue sections. Traditional transcriptomic methods lack the spatial resolution required to sufficiently examine the complex interrelationships between cellular regions in diseased and healthy tissue states. We review the general workflows for ST, from specimen processing to ST data analysis and interpretations of the ST dataset using visualizations and cell deconvolution approaches. We show how recent studies used ST to explore the development or pathogenesis of specific craniofacial regions, including the cranium, palate, salivary glands, tongue, floor of mouth, oropharynx, and periodontium. Analyses of cranial suture patency and palatal fusion during development using ST identified spatial patterns of bone morphogenetic protein in sutures and osteogenic differentiation pathways in the palate, in addition to the discovery of several genes expressed at critical locations during craniofacial development. ST of salivary glands from patients with Sjögren’s disease revealed co-localization of autoimmune antigens with ductal cells and a subpopulation of acinar cells that was specifically depleted by the dysregulated autoimmune response. ST of head and neck lesions, such as premalignant leukoplakia progressing to established oral squamous cell carcinomas, oral cancers with perineural invasions, and oropharyngeal lesions associated with HPV infection spatially profiled the complex tumor microenvironment, showing functionally important gene signatures of tumor cell differentiation, invasion, and nontumor cell dysregulation within patient biopsies. ST also enabled the localization of periodontal disease–associated gene expression signatures within gingival tissues, including genes involved in inflammation, and the discovery of a fibroblast subtype mediating the transition between innate and adaptive immune responses in periodontitis. The increased use of ST, especially in conjunction with single-cell analyses, promises to improve our understandings of craniofacial development and pathogenesis at unprecedented tissue-level resolution in both space and time.

中文翻译：

---

空间转录组学揭示了口腔发病机制的组织复杂性


空间转录组学 （ST） 是一种尖端方法，能够同时分析组织学组织切片内的全局基因表达和空间信息。传统的转录组学方法缺乏充分检查患病和健康组织状态下细胞区域之间复杂相互关系所需的空间分辨率。我们回顾了 ST 的一般工作流程，从样本处理到 ST 数据分析以及使用可视化和细胞反卷积方法解释 ST 数据集。我们展示了最近的研究如何使用 ST 来探索特定颅面区域的发育或发病机制，包括颅骨、上颚、唾液腺、舌、口底、口咽和牙周组织。使用 ST 对发育过程中颅缝通畅和腭融合的分析确定了缝合线中骨形态发生蛋白的空间模式和上颚中的成骨分化途径，此外还发现了颅面发育过程中在关键位置表达的几个基因。干燥病患者唾液腺的 ST 显示自身免疫抗原与导管细胞和腺泡细胞亚群的共定位，该亚群因自身免疫反应失调而特别耗尽。头颈部病变的 ST 点，例如癌前白斑进展为已确诊的口腔鳞状细胞癌、伴有神经周围浸润的口腔癌以及与 HPV 感染相关的口咽病变，在空间上描绘了复杂的肿瘤微环境，显示了患者活检中肿瘤细胞分化、侵袭和非肿瘤细胞失调的重要功能基因特征。 ST 还能够在牙龈组织内定位牙周病相关基因表达特征，包括与炎症有关的基因，并发现介导牙周炎先天免疫反应和适应性免疫反应之间转变的成纤维细胞亚型。ST 的使用增加，尤其是与单细胞分析相结合，有望在空间和时间上以前所未有的组织水平分辨率提高我们对颅面发育和发病机制的理解。