A new murine esophageal organoid culture method and organoid-based model of esophageal squamous cell neoplasia
Biyun Zheng,
Kyung-Pil Ko,
Xuefen Fang,
Xiaozhong Wang,
Jie Zhang,
Sohee Jun,
Bong-Jun Kim,
Wenyi Luo,
Moon Jong Kim,
Youn-Sang Jung,
Christopher L. Cervantes,
Jae-Il Park
Affiliations
Biyun Zheng
Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 0066, Houston, TX 77030, USA; Department of Gastroenterology and Fujian Institute of Digestive Disease, Fujian Medical University Union Hospital, Fuzhou, Fujian 350000, China; Department of Endoscopy Center, Fudan University Shanghai Cancer Center, Shanghai 200032, China
Kyung-Pil Ko
Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 0066, Houston, TX 77030, USA
Xuefen Fang
Department of Gastroenterology and Fujian Institute of Digestive Disease, Fujian Medical University Union Hospital, Fuzhou, Fujian 350000, China
Xiaozhong Wang
Department of Gastroenterology and Fujian Institute of Digestive Disease, Fujian Medical University Union Hospital, Fuzhou, Fujian 350000, China
Jie Zhang
Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 0066, Houston, TX 77030, USA
Sohee Jun
Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 0066, Houston, TX 77030, USA
Bong-Jun Kim
Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 0066, Houston, TX 77030, USA
Wenyi Luo
Department of Life Science, Chung-Ang University, Seoul 06974, Republic of Korea
Moon Jong Kim
Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 0066, Houston, TX 77030, USA
Youn-Sang Jung
Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 0066, Houston, TX 77030, USA; Department of Life Science, Chung-Ang University, Seoul 06974, Republic of Korea
Christopher L. Cervantes
Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 0066, Houston, TX 77030, USA
Jae-Il Park
Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 0066, Houston, TX 77030, USA; Department of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Genetics and Epigenetics Program, MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX 77030, USA; Corresponding author
Summary: Organoids mimic the physiologic and pathologic events of organs. However, no consensus on esophageal organoid (EO) culture methods has been reached. Moreover, organoid models reproducing esophageal squamous cell carcinoma (ESCC) initiation have been unavailable. Herein, we sought to develop an esophageal minimum essential organoid culture medium (E-MEOM) for culturing murine EOs and establishing an early ESCC model. We formulated E-MEOM to grow EOs from a single cell with clonal expansion, maintenance, and passage. We found that EOs cultured in E-MEOM were equivalent to the esophageal epithelium by histological analysis and transcriptomic study. Trp53 knockout and KrasG12D expression in EOs induced the development of esophageal squamous neoplasia, an early lesion of ESCC. Here we propose the new formula for EO culture with minimum components and the organoid model recapitulating ESCC initiation, laying the foundation for ESCC research and drug discovery.
