Haller J, Abedi N, Hafedi A, Shehab O, Wietecha M S
Department of Periodontics, College of Dentistry, University of Illinois Chicago, Chicago, IL, USA.
Department of Oral Biology, College of Dentistry, University of Illinois Chicago, Chicago, IL, USA.
J Dent Res. 2024 Dec;103(13):1331-1339. doi: 10.1177/00220345241271934. Epub 2024 Oct 9.
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.
空间转录组学（ST）是一种前沿方法，能够在组织学组织切片中同时分析全局基因表达和空间信息。传统的转录组学方法缺乏足够的空间分辨率，无法充分研究患病和健康组织状态下细胞区域之间复杂的相互关系。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对ST数据集的解释。我们展示了最近的研究如何利用ST探索特定颅面部区域的发育或发病机制，包括颅骨、腭、唾液腺、舌头、口底、口咽和牙周组织。利用ST分析发育过程中的颅缝通畅性和腭融合，除了发现颅面部发育关键位置表达的几个基因外，还确定了缝中骨形态发生蛋白的空间模式和腭中的成骨分化途径。干燥综合征患者唾液腺的ST显示自身免疫抗原与导管细胞以及腺泡细胞亚群共定位，该亚群在失调的自身免疫反应中特异性减少。对头颈部病变进行ST分析，如从癌前白斑发展为确诊口腔鳞状细胞癌、伴有神经侵犯的口腔癌以及与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，显示了患者活检组织中肿瘤细胞分化、侵袭和非肿瘤细胞失调的功能重要基因特征。ST还能够在牙龈组织中定位与牙周疾病相关的基因表达特征，包括参与炎症的基因，并发现了一种在牙周炎中介导先天免疫和适应性免疫反应转变的成纤维细胞亚型。ST的更多应用，特别是与单细胞分析相结合，有望以前所未有的时空组织水平分辨率提高我们对颅面部发育和发病机制的理解。
