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

doi:10.1126/science.abd1449

GSTDTAP > 气候变化

DOI	10.1126/science.abd1449
	Molecular phenotyping reveals the identity of Barrett’s esophagus and its malignant transition
	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
	2021-08-13
发表期刊	Science
出版年	2021
英文摘要	Many cancers are classified on the basis of the organ or tissue from which they originated. However, identifying the specific cells and conditions that precede tumorigenesis can help us understand and better treat the resulting disease. Nowicki-Osuch et al. used a single-cell approach to investigate the cell of origin for Barrett's esophagus (BE) and the mechanisms leading to the development of esophageal adenocarcinoma (EAC) (see the Perspective by Geboes and Hoorens). Analyses of healthy human esophageal tissues, mutational lineage tracing, and organoid models revealed that BE originates from the gastric cardia and that EAC arises from undifferentiated BE cells. This analysis provides a map of the transcriptional landscape of the healthy esophagus that can be compared with mouse models of disease. Science , abd1449, this issue p. [760][1]; see also abj9797, p. [737][2] 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. [1]: /lookup/doi/10.1126/science.abd1449 [2]: /lookup/doi/10.1126/science.abj9797
领域	气候变化 ; 资源环境
URL	查看原文
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/335878
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Karol Nowicki-Osuch,Lizhe Zhuang,Sriganesh Jammula,等. Molecular phenotyping reveals the identity of Barrett’s esophagus and its malignant transition[J]. Science,2021.
APA	Karol Nowicki-Osuch.,Lizhe Zhuang.,Sriganesh Jammula.,Christopher W. Bleaney.,Krishnaa T. Mahbubani.,...&Rebecca C. Fitzgerald.(2021).Molecular phenotyping reveals the identity of Barrett’s esophagus and its malignant transition.Science.
MLA	Karol Nowicki-Osuch,et al."Molecular phenotyping reveals the identity of Barrett’s esophagus and its malignant transition".Science (2021).