The extracellular matrix controls stem cell specification and crypt morphology in the developing and adult mouse gut.

Autor:	Ramadan R; Laboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.; Oncode Institute, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands., Wouters VM; Laboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.; Oncode Institute, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands., van Neerven SM; Laboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.; Oncode Institute, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands., de Groot NE; Laboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.; Oncode Institute, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands., Garcia TM; Department of Gastroenterology and Hepatology, Tytgat Institute for Intestinal and Liver Research, Amsterdam Gastroenterology Endocrinology and Metabolism, Amsterdam UMC University of Amsterdam, 1015 BK Amsterdam, The Netherlands., Muncan V; Department of Gastroenterology and Hepatology, Tytgat Institute for Intestinal and Liver Research, Amsterdam Gastroenterology Endocrinology and Metabolism, Amsterdam UMC University of Amsterdam, 1015 BK Amsterdam, The Netherlands., Franklin OD; The Medical College of Wisconsin, Department of Cell Biology, Neurobiology, and Anatomy, Milwaukee, WI 53226, USA., Battle M; The Medical College of Wisconsin, Department of Cell Biology, Neurobiology, and Anatomy, Milwaukee, WI 53226, USA., Carlson KS; The Medical College of Wisconsin, Department of Cell Biology, Neurobiology, and Anatomy, Milwaukee, WI 53226, USA.; The Blood Research Institute of Wisconsin, part of Versiti, and the Medical College of Wisconsin, Department of Internal Medicine, Milwaukee, WI 53226, USA., Leach J; Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK.; Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Glasgow, G61 1QH, UK., Sansom OJ; Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK.; Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Glasgow, G61 1QH, UK., Boulard O; CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - Centre d'Infection et d'Immunité de Lille (CIIL), Université de Lille, 59019 Lille, France., Chamaillard M; CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - Centre d'Infection et d'Immunité de Lille (CIIL), Université de Lille, 59019 Lille, France., Vermeulen L; Laboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.; Oncode Institute, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands., Medema JP; Laboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.; Oncode Institute, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands., Huels DJ; Laboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.; Oncode Institute, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
Jazyk:	angličtina
Zdroj:	Biology open [Biol Open] 2022 Dec 15; Vol. 11 (12). Date of Electronic Publication: 2022 Nov 23.
DOI:	10.1242/bio.059544
Abstrakt:	The rapid renewal of the epithelial gut lining is fuelled by stem cells that reside at the base of intestinal crypts. The signal transduction pathways and morphogens that regulate intestinal stem cell self-renewal and differentiation have been extensively characterised. In contrast, although extracellular matrix (ECM) components form an integral part of the intestinal stem cell niche, their direct influence on the cellular composition is less well understood. We set out to systematically compare the effect of two ECM classes, the interstitial matrix and the basement membrane, on the intestinal epithelium. We found that both collagen I and laminin-containing cultures allow growth of small intestinal epithelial cells with all cell types present in both cultures, albeit at different ratios. The collagen cultures contained a subset of cells enriched in fetal-like markers. In contrast, laminin increased Lgr5+ stem cells and Paneth cells, and induced crypt-like morphology changes. The transition from a collagen culture to a laminin culture resembled gut development in vivo. The dramatic ECM remodelling was accompanied by a local expression of the laminin receptor ITGA6 in the crypt-forming epithelium. Importantly, deletion of laminin in the adult mouse resulted in a marked reduction of adult intestinal stem cells. Overall, our data support the hypothesis that the formation of intestinal crypts is induced by an increased laminin concentration in the ECM. Competing Interests: Competing interests L.V. received consultancy fees from Bayer, MSD, Genentech, Servier and Pierre Fabre, but these had no relation to the content of this publication. (© 2022. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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