2021年8月13日，英国剑桥大学Rebecca C. Fitzgerald团队在《科学》杂志发表论文，利用分子表型分析揭示了巴雷特食管的特征及其恶性转变机制。

为了解决巴雷特食管癌细胞起源问题，研究人员从健康和患者供体中采集了跨胃食管连接处的组织，包括分离食管粘膜下腺。利用单细胞转录组学分析、甲基化计算机谱系追踪、开放染色质和体细胞突变分析以及类器官模型功能研究分析相组合的方法，研究发现c-MYC和HNF4A驱动的巴雷特食管转录程序起源于贲门。

此外，该数据表明，即使没有病理学可识别的组织转化前体，食管腺癌也可能来源于未分化的巴雷特食管细胞类型。该研究提供了雷特食管癌的早期检测策略。

据了解，人们对恶行细胞的起源及其致癌倾向知之甚少。巴雷特食管是一种常见的组织转化性疾病，会增加食管腺癌的患病风险，但其细胞起源不明。

附：英文原文

Title: Molecular phenotyping reveals the identity of Barrett’s esophagus and its malignant transition

Author: Karol Nowicki-Osuch, Lizhe Zhuang, Sriganesh Jammula, Christopher W. Bleaney, Krishnaa T. Mahbubani, Ginny Devonshire, Annalise Katz-Summercorn, Nils Eling, Anna Wilbrey-Clark, Elo Madissoon, John Gamble, Massimiliano Di Pietro, Maria O’Donovan, Kerstin B. Meyer, Kourosh Saeb-Parsy, Andrew D. Sharrocks, Sarah A. Teichmann, John C. Marioni, Rebecca C. Fitzgerald

Issue&Volume: 2021/08/13

Abstract: The origin of human metaplastic states and their propensity for cancer is poorly understood. Barrett’s esophagus is a common metaplastic condition that increases the risk for esophageal adenocarcinoma, and its cellular origin is enigmatic. To address this, we harvested tissues spanning the gastroesophageal junction from healthy and diseased donors, including isolation of esophageal submucosal glands. A combination of single-cell transcriptomic profiling, in silico lineage tracing from methylation, open chromatin and somatic mutation analyses, and functional studies in organoid models showed that Barrett’s esophagus originates from gastric cardia through c-MYC and HNF4A-driven transcriptional programs. Furthermore, our data indicate that esophageal adenocarcinoma likely arises from undifferentiated Barrett’s esophagus cell types even in the absence of a pathologically identifiable metaplastic precursor, illuminating early detection strategies.

DOI: 10.1126/science.abd1449

Source: https://science.sciencemag.org/content/373/6556/760