Cell Reports (Jul 2020)
Cycling Stem Cells Are Radioresistant and Regenerate the Intestine
- Xiaole Sheng,
- Ziguang Lin,
- Cong Lv,
- Chunlei Shao,
- Xueyun Bi,
- Min Deng,
- Jiuzhi Xu,
- Christian F. Guerrero-Juarez,
- Mengzhen Li,
- Xi Wu,
- Ran Zhao,
- Xu Yang,
- Guilin Li,
- Xiaowei Liu,
- Qingyu Wang,
- Qing Nie,
- Wei Cui,
- Shan Gao,
- Hongquan Zhang,
- Zhihua Liu,
- Yingzi Cong,
- Maksim V. Plikus,
- Christopher J. Lengner,
- Bogi Andersen,
- Fazheng Ren,
- Zhengquan Yu
Affiliations
- Xiaole Sheng
- Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, Department of Nutrition and Health, College of Biological Sciences, China Agricultural University, Beijing 100193, China
- Ziguang Lin
- Departments of Medicine and Biological Chemistry, University of California, Irvine School of Medicine, Irvine, CA 92697, USA
- Cong Lv
- Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, Department of Nutrition and Health, College of Biological Sciences, China Agricultural University, Beijing 100193, China
- Chunlei Shao
- Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, Department of Nutrition and Health, College of Biological Sciences, China Agricultural University, Beijing 100193, China
- Xueyun Bi
- Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, Department of Nutrition and Health, College of Biological Sciences, China Agricultural University, Beijing 100193, China
- Min Deng
- Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, Department of Nutrition and Health, College of Biological Sciences, China Agricultural University, Beijing 100193, China
- Jiuzhi Xu
- Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, Department of Nutrition and Health, College of Biological Sciences, China Agricultural University, Beijing 100193, China
- Christian F. Guerrero-Juarez
- Department of Mathematics, NSF-Simons Center for Multiscale Cell Fate Research, University of California, Irvine, Irvine, CA 92697, USA; Department of Developmental and Cell Biology, Sue and Bill Gross Stem Cell Research, Center for Complex Biological Systems, University of California, Irvine, Irvine, CA 92697, USA
- Mengzhen Li
- Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, Department of Nutrition and Health, College of Biological Sciences, China Agricultural University, Beijing 100193, China
- Xi Wu
- Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, Department of Nutrition and Health, College of Biological Sciences, China Agricultural University, Beijing 100193, China
- Ran Zhao
- Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, Department of Nutrition and Health, College of Biological Sciences, China Agricultural University, Beijing 100193, China
- Xu Yang
- Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, Department of Nutrition and Health, College of Biological Sciences, China Agricultural University, Beijing 100193, China
- Guilin Li
- Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, Department of Nutrition and Health, College of Biological Sciences, China Agricultural University, Beijing 100193, China
- Xiaowei Liu
- Department of Gastroenterology, Xiangya Hospital of Central South University, Changsha 410008, Hunan, China
- Qingyu Wang
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing, China
- Qing Nie
- Department of Mathematics, NSF-Simons Center for Multiscale Cell Fate Research, University of California, Irvine, Irvine, CA 92697, USA
- Wei Cui
- Institute of Reproductive and Developmental Biology, Faculty of Medicine, Imperial College London, London, UK
- Shan Gao
- CAS Key Laboratory of Bio-medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, Jiangsu 215163, China
- Hongquan Zhang
- Laboratory of Molecular Cell Biology and Tumor Biology, Department of Anatomy, Histology and Embryology, Beijing 100191, China
- Zhihua Liu
- State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, Beijing 100021, China
- Yingzi Cong
- Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA
- Maksim V. Plikus
- Department of Developmental and Cell Biology, Sue and Bill Gross Stem Cell Research, Center for Complex Biological Systems, University of California, Irvine, Irvine, CA 92697, USA
- Christopher J. Lengner
- Department of Biomedical Sciences, School of Veterinary Medicine, and Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Bogi Andersen
- Departments of Medicine and Biological Chemistry, University of California, Irvine School of Medicine, Irvine, CA 92697, USA
- Fazheng Ren
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing, China; Corresponding author
- Zhengquan Yu
- Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, Department of Nutrition and Health, College of Biological Sciences, China Agricultural University, Beijing 100193, China; Corresponding author
- Journal volume & issue
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Vol. 32,
no. 4
p. 107952
Abstract
Summary: A certain number of epithelial cells in intestinal crypts are DNA damage resistant and contribute to regeneration. However, the cellular mechanism underlying intestinal regeneration remains unclear. Using lineage tracing, we show that cells marked by an Msi1 reporter (Msi1+) are right above Lgr5high cells in intestinal crypts and exhibit DNA damage resistance. Single-cell RNA sequencing reveals that the Msi1+ cells are heterogeneous with the majority being intestinal stem cells (ISCs). The DNA damage-resistant subpopulation of Msi1+ cells is characterized by low-to-negative Lgr5 expression and is more rapidly cycling than Lgr5high radiosensitive crypt base columnar stem cells (CBCs). This enables an efficient repopulation of the intestinal epithelium at early stage when Lgr5high cells are not emerging. Furthermore, relative to CBCs, Msi1+ cells preferentially produce Paneth cells during homeostasis and upon radiation repair. Together, we demonstrate that the DNA damage-resistant Msi1+ cells are cycling ISCs that maintain and regenerate the intestinal epithelium.
