Understanding the development of oral epithelial organs through single cell transcriptomic analysis.

Understanding the development of oral epithelial organs through single cell transcriptomic analysis.
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DOI:
10.1242/dev.200539
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发表时间:
2022-08-15
期刊:
Development (Cambridge, England)
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在颅面发育期间,口腔上皮从形态上均一的组织开始,产生局部复杂的结构,包括牙齿、唾液腺和味蕾。上皮细胞最初是如何构筑图案并被指定为产生不同类型的细胞的,目前还很大程度上尚不清楚。为了阐明指导不同口腔上皮细胞群形成的遗传程序,我们绘制了胚胎第12天小鼠下颌上皮细胞在单细胞分辨率下的转录图谱。我们的分析确定了定义不同上皮细胞类型的关键转录因子和基因调控网络。通过研究口腔-流产轴的时空图案化过程,我们的结果提出了一个模型,在该模型中,牙场通过前面的流产上皮和后面的非牙齿口腔上皮的形成而逐渐限制在它的位置。利用我们的数据,我们还发现NTRK2是形成门牙的增殖驱动因素,有助于其内陷。总之,我们的结果提供了胚胎下颌上皮的详细转录图谱,并揭示了在各种口腔上皮结构规范过程中存在的新的遗传标记和调节因子。摘要:对胚胎小鼠下颌外胚层的单细胞分析确定了具有明确基因调控网络的不同群体,并揭示了在口腔-流产模式形成过程中逐渐形成的上皮区。
During craniofacial development, the oral epithelium begins as a morphologically homogeneous tissue that gives rise to locally complex structures, including the teeth, salivary glands and taste buds. How the epithelium is initially patterned and specified to generate diverse cell types remains largely unknown. To elucidate the genetic programs that direct the formation of distinct oral epithelial populations, we mapped the transcriptional landscape of embryonic day 12 mouse mandibular epithelia at single cell resolution. Our analysis identified key transcription factors and gene regulatory networks that define different epithelial cell types. By examining the spatiotemporal patterning process along the oral-aboral axis, our results propose a model in which the dental field is progressively confined to its position by the formation of the aboral epithelium anteriorly and the non-dental oral epithelium posteriorly. Using our data, we also identified Ntrk2 as a proliferation driver in the forming incisor, contributing to its invagination. Together, our results provide a detailed transcriptional atlas of the embryonic mandibular epithelium, and unveil new genetic markers and regulators that are present during the specification of various oral epithelial structures. Summary: Single cell analysis of embryonic mouse mandibular ectoderm identifies distinct populations with defined gene regulatory networks and unveils epithelial zones that form progressively during oral-aboral patterning.
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