한빛사논문
University Medical Centre Utrecht, Hubrecht Institute, University of Cambridge
Abstract
Daniel E. Stange1, 2, 8, Bon-Kyoung Koo1, 3, 8, Meritxell Huch1, Greg Sibbel4, Onur Basak1, Anna Lyubimova1, 5, Pekka Kujala6, Sina Bartfeld1, Jan Koster7, Jessica H. Geahlen4, Peter J. Peters6, Johan H. van Es1, Marc van de Wetering1, Jason C. Mills4, Hans Clevers1
1 Hubrecht Institute for Developmental Biology and Stem Cell Research & University Medical Centre Utrecht, 3584 CT Utrecht, the Netherlands
2 Department of General, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, University of Dresden, 01307 Dresden, Germany
3 Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge CB2 1QR, UK
4 Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
5 Department of Physics & Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
6 Division of Cell Biology II, Antoni van Leeuwenhoek Hospital/Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands
7 Department of Oncogenomics, Academic Medical Center, University of Amsterdam, 1100 DE Amsterdam, the Netherlands
8 These authors contributed equally to this work
Corresponding author : Hans Clevers
Summary
Proliferation of the self-renewing epithelium of the gastric corpus occurs almost exclusively in the isthmus of the glands, from where cells migrate bidirectionally toward pit and base. The isthmus is therefore generally viewed as the stem cell zone. We find that the stem cell marker Troy is expressed at the gland base by a small subpopulation of fully differentiated chief cells. By lineage tracing with a Troy-eGFP-ires-CreERT2 allele, single marked chief cells are shown to generate entirely labeled gastric units over periods of months. This phenomenon accelerates upon tissue damage. Troy+ chief cells can be cultured to generate long-lived gastric organoids. Troy marks a specific subset of chief cells that display plasticity in that they are capable of replenishing entire gastric units, essentially serving as quiescent “reserve” stem cells. These observations challenge the notion that stem cell hierarchies represent a “one-way street.”
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