Single-Cell Transcriptomes Reveal a Complex Cellular Landscape in the Middle Ear and Differential Capacities for Acute Response to Infection
Single-Cell Transcriptomes Reveal a Complex Cellular Landscape in the Middle Ear and Differential Capacities for Acute Response to Infection
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DOI：
10.3389/fgene.2020.00358
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发表时间：
2020-04-15
影响因子：
3.7
通讯作者：
Kurabi, Arwa
中科院分区：
文献类型：
--
作者：
Ryan, Allen F.;Nasamran, Chanond A.;Kurabi, Arwa
使用单细胞转录组学分析正常小鼠中耳的细胞。聚类分析6770转录组确定了17个细胞簇对应于不同的细胞类型：5上皮细胞，3间质细胞，3淋巴细胞，2单核细胞，2内皮细胞，一周细胞和一个黑素细胞簇。在一些簇内，鉴定了细胞亚型。虽然许多对应于先前研究中已知的细胞类型，但注意到了几种新的类型或亚型。结果表明，在静止的中耳粘膜内存在意想不到的细胞多样性。单纯急性中耳炎的消退太快，同源免疫不能发挥主要作用。因此，先天免疫可能是中耳感染正常恢复的原因。对病原体的快速反应的需要表明先天免疫基因可能由中耳细胞组成型表达。因此，我们评估了所有细胞类型中先天免疫基因的表达，以评估对中耳感染快速反应的潜力。常驻单核细胞/巨噬细胞表达的此类基因最多，包括病原体受体、细胞因子、趋化因子和趋化因子受体。其他细胞类型显示出不同的先天免疫基因谱。上皮细胞优先表达病原体受体、杀菌肽和粘蛋白。基质和内皮细胞表达病原体受体。周细胞表达促炎细胞因子。淋巴细胞表达趋化因子受体和抗菌剂。结果表明，组织单核细胞，包括巨噬细胞，是中耳对感染的直接反应的主要调节者，但实际上所有细胞类型都在协同作用，以抵御病原体。
Single-cell transcriptomics was used to profile cells of the normal murine middle ear. Clustering analysis of 6770 transcriptomes identified 17 cell clusters corresponding to distinct cell types: five epithelial, three stromal, three lymphocyte, two monocyte, two endothelial, one pericyte and one melanocyte cluster. Within some clusters, cell subtypes were identified. While many corresponded to those cell types known from prior studies, several novel types or subtypes were noted. The results indicate unexpected cellular diversity within the resting middle ear mucosa. The resolution of uncomplicated, acute, otitis media is too rapid for cognate immunity to play a major role. Thus innate immunity is likely responsible for normal recovery from middle ear infection. The need for rapid response to pathogens suggests that innate immune genes may be constitutively expressed by middle ear cells. We therefore assessed expression of innate immune genes across all cell types, to evaluate potential for rapid responses to middle ear infection. Resident monocytes/macrophages expressed the most such genes, including pathogen receptors, cytokines, chemokines and chemokine receptors. Other cell types displayed distinct innate immune gene profiles. Epithelial cells preferentially expressed pathogen receptors, bactericidal peptides and mucins. Stromal and endothelial cells expressed pathogen receptors. Pericytes expressed pro-inflammatory cytokines. Lymphocytes expressed chemokine receptors and antimicrobials. The results suggest that tissue monocytes, including macrophages, are the master regulators of the immediate middle ear response to infection, but that virtually all cell types act in concert to mount a defense against pathogens.