A matter of differentiation: equine enteroids as a model for the in vivo intestinal epithelium

• DOI: 10.1186/s13567-024-01283-0
• Publication Date: 2024-03-16T10:01:54Z
• Authors: Christina Windhaber; Anna Heckl; Georg Csukovich; Barbara Pratscher; Iwan Anton Burgener; Nora Biermann; Franziska Dengler
• Keywords: Intestinal epithelium; Enterocyte; Goblet cell; Enteroendocrine cell; Intestinal mucosa

Abstract Epithelial damage due to gastrointestinal disorders frequently causes severe disease in horses. To study the underlying pathophysiological processes, we aimed establish equine jejunum and colon enteroids (eqJE, eqCE) mimicking vivo epithelium. Therefore, were cultivated four different media for differentiation subsequently characterized histomorphologically, on mRNA protein level comparison native epithelium of same donor horses identify ideal culture conditions an vitro model system. With increasing enterocyte differentiation, showed a reduced growth rate as well predominantly spherical morphology less budding compared proliferation medium. Combined or individual withdrawal stem cell niche pathway components resulted lower expression levels markers concomitant enterocytes, goblet cells enteroendocrine cells. For eqCE, Wnt alone was sufficient generation differentiated enterocytes with close resemblance removal Wnt, R-spondin Noggin addition DAPT stimulated eqJE at similar epithelium, particularly regard enterocytes. In summary, successfully defined medium composition that promotes formation eqCE consisting multiple types resembling Our findings emphasize importance adapting respective species intestinal segment. This will be used investigate pathological mechanisms future studies.