한빛사 논문
University of Cambridge, IMBA - Institute of Molecular Biotechnology
Seungmin Han1,2,14, Juergen Fink1,3,14, David J. Jörg2,4,15, Eunmin Lee5,15, Min Kyu Yum1,2,15, Lemonia Chatzeli1,2,15, Sebastian R. Merker6,15, Manon Josserand1,15, Teodora Trendafilova1, Amanda Andersson-Rolf1,3, Catherine Dabrowska1, Hyunki Kim1, Ronald Naumann7, Ji-Hyun Lee8, Nobuo Sasaki9, Richard Lester Mort10, Onur Basak11,13, Hans Clevers11, Daniel E. Stange6, Anna Philpott1,12, Jong Kyoung Kim5,*, Benjamin D. Simons1,2,4,16,*, Bon-Kyoung Koo1,3,8,16,17,*
1 Wellcome Trust–Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge CB2 1QR, UK
2 The Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, UK
3 Department of Genetics, University of Cambridge, Cambridge CB2 3EH, UK
4 Department of Applied Mathematics and Theoretical Physics, Centre for Mathematical Sciences, University of Cambridge, Wilberforce Road, Cambridge CB3 0WA, UK
5 Department of New Biology, DGIST, Daegu 42988, Republic of Korea
6 Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Fetscherstr. 74, 01307 Dresden, Germany
7 MPI of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany
8 Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter (VBC), Dr. Bohr-Gasse 3, 1030 Vienna, Austria
9 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
10 Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Furness Building, Lancaster University, Bailrigg, Lancaster LA1 4YG, UK
11 Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center Utrecht, 3584 Utrecht, the Netherlands
12 Department of Oncology, Hutchison/MRC Research Centre, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0XZ, UK
13Present address: Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht and Utrecht University, Universiteitsweg 100, 3584 Utrecht, the Netherlands
14These authors contributed equally
15These authors contributed equally
16These authors contributed equally
17Lead Contact
*Corresponding author : Jong Kyoung Kim, Benjamin D. Simons, Bon-Kyoung Koo
Abstract
The gastric corpus epithelium is the thickest part of the gastrointestinal tract and is rapidly turned over. Several markers have been proposed for gastric corpus stem cells in both isthmus and base regions. However, the identity of isthmus stem cells (IsthSCs) and the interaction between distinct stem cell populations is still under debate. Here, based on unbiased genetic labeling and biophysical modeling, we show that corpus glands are compartmentalized into two independent zones, with slow-cycling stem cells maintaining the base and actively cycling stem cells maintaining the pit-isthmus-neck region through a process of “punctuated” neutral drift dynamics. Independent lineage tracing based on Stmn1 and Ki67 expression confirmed that rapidly cycling IsthSCs maintain the pit-isthmus-neck region. Finally, single-cell RNA sequencing (RNA-seq) analysis is used to define the molecular identity and lineage relationship of a single, cycling, IsthSC population. These observations define the identity and functional behavior of IsthSCs.
Keywords : gastric corpus isthmus stem cell; two stem cell compartments; punctuated neutral drift; unbiased genetic labeling; deep tissue imaging; biophysical modeling; single-cell RNA-seq; Lgr5; Troy; intestine
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