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The extracellular matrix controls stem cell specification and crypt morphology in the developing and adult mouse gut. Biol Open 2022 Dec 15;11(12)

Date

11/10/2022

Pubmed ID

36350252

Pubmed Central ID

PMC9713296

DOI

10.1242/bio.059544

Scopus ID

2-s2.0-85142918558 (requires institutional sign-in at Scopus site)   4 Citations

Abstract

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.

Author List

Ramadan R, Wouters VM, van Neerven SM, de Groot NE, Garcia TM, Muncan V, Franklin OD, Battle M, Carlson KS, Leach J, Sansom OJ, Boulard O, Chamaillard M, Vermeulen L, Medema JP, Huels DJ

Author

Karen-Sue B. Carlson MD, PhD Associate Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Collagen
Extracellular Matrix
Intestines
Laminin
Mice
Paneth Cells
Stem Cells