Modeling colorectal tumorigenesis using the organoids derived from conditionally immortalized mouse intestinal crypt cells (ciMICs)

Xiaoxing Wu; Zhaoxia Li; Hongyu Zhang; Fang He; Min Qiao; Huaxiu Luo; Jing Zhang; Meng Zhang; Yukun Mao; William Wagstaff; Yongtao Zhang; Changchun Niu; Xia Zhao; Hao Wang; Linjuan Huang; Deyao Shi; Qing Liu; Na Ni; Ning Wang

doi:10.1016/j.gendis.2021.01.004

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Modeling colorectal tumorigenesis using the organoids derived from conditionally immortalized mouse intestinal crypt cells (ciMICs)

Full-length article | 更新时间：2022-06-24

- Modeling colorectal tumorigenesis using the organoids derived from conditionally immortalized mouse intestinal crypt cells (ciMICs)
- Modeling colorectal tumorigenesis using the organoids derived from conditionally immortalized mouse intestinal crypt cells (ciMICs)
- Genes & Diseases 2021年8卷第6期
- 作者机构：
  
  1. Departments of Gastrointestinal Surgery, Medicine/Gastroenterology, and Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University,Chongqing,PR China,400016
  2. Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center,IL,Chicago,USA,606037
  3. Department of Oncology, The PLA Rocket Force Characteristic Medical Center,Beijing,PR China,100088
  4. Departments of Burn & Plastic Surgery, West China Hospital of Sichuan University,Sichuan Province,Chengdu,PR China,610041
  5. Department of Orthopaedic Surgery, The First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangdong Province,Guangzhou,PR China,510405
  6. Departments of Orthopaedic Surgery, The Affiliated Zhongnan Hospital of Wuhan University,Hubei Province,Wuhan,PR China,430071
  7. Department of Orthopaedic Surgery, The Affiliated Hospital of Qingdao University,Shandong Province,Qingdao,PR China,266000
  8. Department of Clinical Laboratory Medicine, Chongqing General Hospital Affiliated with the University of Chinese Academy of Sciences,Chongqing,PR China,400013
  9. Ministry of Education Key Laboratory of Diagnostic Medicine, and the School of Laboratory Diagnostic Medicine, Chongqing Medical University,Chongqing,PR China,400016
  10. Department of Orthopaedics, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology,Hubei Province,Wuhan,PR China,430022
  11. Department of Spine Surgery, Second Xiangya Hospital, Central South University,Hunan Province,Changsha,PR China,410008
- 作者简介：
- 基金信息：
- DOI：10.1016/j.gendis.2021.01.004
  中图分类号：
- 纸质出版日期：2021，
  
  网络出版日期：2021-11-1，
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Xiaoxing Wu, Zhaoxia Li, Hongyu Zhang, 等. Modeling colorectal tumorigenesis using the organoids derived from conditionally immortalized mouse intestinal crypt cells (ciMICs)[J]. Genes & Diseases, 2021,8(6).

Xiaoxing Wu, Zhaoxia Li, Hongyu Zhang, et al. Modeling colorectal tumorigenesis using the organoids derived from conditionally immortalized mouse intestinal crypt cells (ciMICs)[J]. Genes & Diseases, 2021,8(6).
Xiaoxing Wu, Zhaoxia Li, Hongyu Zhang, 等. Modeling colorectal tumorigenesis using the organoids derived from conditionally immortalized mouse intestinal crypt cells (ciMICs)[J]. Genes & Diseases, 2021,8(6). DOI： 10.1016/j.gendis.2021.01.004.

Xiaoxing Wu, Zhaoxia Li, Hongyu Zhang, et al. Modeling colorectal tumorigenesis using the organoids derived from conditionally immortalized mouse intestinal crypt cells (ciMICs)[J]. Genes & Diseases, 2021,8(6). DOI： 10.1016/j.gendis.2021.01.004.

摘要

Abstract

Intestinal cancers are developed from intestinal epithelial stem cells (ISCs) in intestinal crypts through a multi-step process involved in genetic mutations of oncogenes and tumor suppressor genes. ISCs play a key role in maintaining the homeostasis of gut epithelium. In 2009

Sato et al established a three-dimensional culture system

which mimicked the niche microenvironment by employing the niche factors

and successfully grew crypt ISCs into organoids or Mini-guts

in vitro

. Since then

the intestinal organoid technology has been used to delineate cellular signaling in ISC biology. However

the cultured organoids consist of heterogeneous cell populations

and it was technically challenging to introduce genomic changes into three-dimensional organoids. Thus

there was a technical necessity to develop a two-dimensional ISC culture system for effective genomic manipulations. In this study

we established a conditionally immortalized mouse intestinal crypt (ciMIC) cell line by using a

piggyBac

transposon-based SV40 T antigen expression system. We showed that the ciMICs maintained long-term proliferative activity under two-dimensional niche factor-containing culture condition

retained the biological characteristics of intestinal epithelial stem cells

and could form intestinal organoids in three-dimensional culture. While

in vivo

cell implantation tests indicated that the ciMICs were non-tumorigenic

the ciMICs overexpressing oncogenic β-catenin and/or KRAS exhibited high proliferative activity and developed intestinal adenoma-like pathological features

in vivo

. Collectively

these findings strongly suggested that the engineered ciMICs should be used as a valuable tool cell line to dissect the genetic and/or epigenetic underpinnings of intestinal tumorigenesis.

关键词

Keywords

Cancer modelingConditional immortalizationMini-gut organoidsMouse intestinal crypt (MIC) cellsTumorigenesis

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