Eosinophilic esophagitis-associated epithelial remodeling may limit esophageal carcinogenesis.
Eosinophilic esophagitis-associated epithelial remodeling may limit esophageal carcinogenesis.
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DOI：
10.3389/falgy.2023.1086032
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发表时间：
2023
影响因子：
--
通讯作者：
Whelan, Kelly A.
中科院分区：
文献类型：
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作者：
Fuller, Annie D.;Karami, Adam L.;Kabir, Mohammad Faujul;Klochkova, Alena;Jackson, Jazmyne L.;Mu, Anbin;Tan, Yinfei;Klein-Szanto, Andres J.;Whelan, Kelly A.
关键词：
在稳态条件下，食管上皮显示增殖/分化梯度，其产生为增殖基底细胞产生基底上细胞，然后是终末分化的表面细胞。这种增殖/分化梯度在食管病理学中经常受到干扰。基底细胞增生可能发生在胃食管反流病（GERD）或嗜酸性食管炎（EoE）患者中，胃食管反流病是一种胃酸进入食管的疾病，嗜酸性食管炎是一种新出现的食物过敏形式。虽然GERD是食管癌的主要风险因素，但流行病学数据表明EoE患者不会发生食管癌。为了研究EoE和食管癌对食管上皮细胞景观的影响，我们在EoE和食管癌，特别是食管鳞状细胞癌（ESCC）的小鼠模型中进行单细胞RNA测序。我们进一步评估了EoE和ESCC富集的上皮细胞簇中共表达基因的模块。最后，我们配对EoE和ESCC小鼠模型来研究这些病理之间的功能关系。在患有EoE或ESCC的小鼠中，我们发现与正常食管上皮相比，细胞群扩增。在EoE小鼠中，我们检测到4个基底上群体的明显扩增，同时2个基底群体的耗竭。相比之下，患有ESCC的小鼠显示2个基底群和1个基底上群的独特扩增，以及2个基底上群的耗竭。衰老、糖皮质激素受体信号传导和粒细胞-巨噬细胞集落刺激因子途径与EoE富集簇相关，而与细胞增殖和代谢相关的途径在ESCC富集簇中被鉴定。最后，我们的体内数据表明，暴露于EoE炎症限制了食管癌发生的肿瘤负荷。我们的研究结果提供了EoE和食管癌之间的关系的第一个功能性调查，并建议EoE炎症反应中发生的食管上皮重塑事件可能会限制食管癌的发生。这项研究可能对利用过敏性炎症相关的上皮生物学改变来预防和/或治疗食管癌具有未来的意义。
Under homeostatic conditions, esophageal epithelium displays a proliferation/differentiation gradient that is generated as proliferative basal cells give rise to suprabasal cells then terminally differentiated superficial cells. This proliferation/differentiation gradient is often perturbed in esophageal pathologies. Basal cell hyperplasia may occur in patients with gastroesophageal reflux disease (GERD), a condition in which acid from the stomach enters the esophagus, or eosinophilic esophagitis (EoE), an emerging form of food allergy. While GERD is a primary risk factor for esophageal cancer, epidemiological data suggests that EoE patients do not develop esophageal cancer. In order to investigate the impact of EoE and esophageal cancer specifically on the cellular landscape of esophageal epithelium, we perform single cell RNA-sequencing in murine models of EoE and esophageal cancer, specifically esophageal squamous cell carcinoma (ESCC). We further evaluate modules of co-expressed genes in EoE- and ESCC-enriched epithelial cell clusters. Finally, we pair EoE and ESCC murine models to examine the functional relationship between these pathologies. In mice with either EoE or ESCC, we find expansion of cell populations as compared to normal esophageal epithelium. In mice with EoE, we detect distinct expansion of 4 suprabasal populations coupled with depletion of 2 basal populations. By contrast, mice with ESCC display unique expansion of 2 basal populations and 1 suprabasal population, as well as depletion of 2 suprabasal populations. Senescence, glucocorticoid receptor signaling, and granulocyte-macrophage colony-stimulating factor pathways are associated with EoE-enriched clusters while pathways associated with cell proliferation and metabolism are identified in ESCC-enriched clusters. Finally, our in vivo data demonstrate that exposure to EoE inflammation limits tumor burden of esophageal carcinogenesis. Our findings provide the first functional investigation of the relationship between EoE and esophageal cancer and suggest that esophageal epithelial remodeling events occurring in response to EoE inflammation may limit esophageal carcinogenesis. This investigation may have future implications for leveraging allergic inflammation-associated alterations in epithelial biology to prevent and/or treat esophageal cancer.
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影响因子：
16.6
作者：
Chatterjee J;Sanapala S;Cobb O;Bewley A;Goldstein AK;Cordell E;Ge X;Garbow JR;Holtzman MJ;Gutmann DH
通讯作者：
Gutmann DH
影响因子：
9.8
作者：
Dellon, Evan S.;Chen, Xiaoxin;Miller, C. Ryan;Fritchie, Karen J.;Rubinas, Tara C.;Woosley, John T.;Shaheen, Nicholas J.
通讯作者：
Shaheen, Nicholas J.
影响因子：
29.4
作者：
Akei, HS;Mishra, A;Rothenberg, ME
通讯作者：
Rothenberg, ME
影响因子：
7.2
作者：
Lucarini, Valeria;Ziccheddu, Giovanna;Schiavoni, Giovanna
通讯作者：
Schiavoni, Giovanna
单细胞转录组分析揭示了鼠食管上皮的细胞多样性。
影响因子：
16.6
作者：
通讯作者：
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