The olfactory neuroepithelium serves as a sensory organ for odors and forms part of the nasal mucosal barrier. Olfactory sensory neurons are surrounded and supported by epithelial cells. Among them, microvillous cells (MVCs) are strategically positioned at the apical surface, but their specific functions are enigmatic, and their relationship to the other specialized epithelial cells is unclear. Here, we establish that the family of MVCs comprises tuft cells and ionocytes in both mice and humans. Integrating analysis of the respiratory and olfactory epithelia, we define the distinct receptor expression of TRPM5 + tuft-MVCs compared with Gɑ-gustducin high respiratory tuft cells and characterize a previously undescribed population of glandular DCLK1 + tuft cells. To establish how allergen sensing by tuft-MVCs might direct olfactory mucosal responses, we used an integrated single-cell transcriptional and protein analysis. Inhalation of Alternaria induced mucosal epithelial effector molecules including Chil4 and a distinct pathway leading to proliferation of the quiescent olfactory horizontal basal stem cell (HBC) pool, both triggered in the absence of olfactory apoptosis. Alternaria- and ATP-elicited HBC proliferation was dependent on TRPM5 + tuft-MVCs, identifying these specialized epithelial cells as regulators of olfactory stem cell responses. Together, our data provide high-resolution characterization of nasal tuft cell heterogeneity and identify a function of TRPM5 + tuft-MVCs in directing the olfactory mucosal response to allergens.

中文翻译：

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鼻细胞图谱揭示簇细胞的异质性及其在指导嗅觉干细胞增殖中的作用

嗅觉神经上皮作为气味的感觉器官，并形成鼻粘膜屏障的一部分。嗅觉感觉神经元被上皮细胞包围和支持。其中，微绒毛细胞（MVC）战略性地位于顶端表面，但它们的具体功能是神秘的，并且它们与其他特化上皮细胞的关系尚不清楚。在这里，我们确定 MVC 家族由小鼠和人类的簇细胞和离子细胞组成。综合呼吸和嗅觉上皮细胞的分析，我们定义了 TRPM5 的独特受体表达+tuft-MVC 与 Gɑ-gustducin 相比高的呼吸簇细胞并表征了先前未描述的腺体 DCLK1 群体+簇状细胞。为了确定簇状 MVC 的过敏原传感如何指导嗅觉粘膜反应，我们使用了集成的单细胞转录和蛋白质分析。吸入链格孢属诱导的粘膜上皮效应分子包括奇尔4以及导致静态嗅觉水平基底干细胞（HBC）池增殖的独特途径，两者都是在没有嗅觉细胞凋亡的情况下触发的。链格孢属-ATP 引发的 HBC 增殖依赖于 TRPM5+tuft-MVC，将这些特殊的上皮细胞识别为嗅觉干细胞反应的调节者。总之，我们的数据提供了鼻簇细胞异质性的高分辨率特征并确定了 TRPM5 的功能+tuft-MVC 引导嗅觉粘膜对过敏原的反应。