Colonic CD90+ Crypt Fibroblasts Secrete Semaphorins to Support Epithelial Growth

摘要

Intestinal epithelial cells have a defined hierarchy withstem cells located at the bottom of the crypt and differentiatedcells more at the top. Epithelial cell renewaland differentiation are strictly controlled by variousregulatory signals provided by epithelial as well as surroundingcells. Although there is evidence that stromalcells contribute to the intestinal stem cell niche, theirmarkers and the soluble signals they produce havebeen incompletely defined. Using a number of establishedstromal cell markers, we phenotypically andfunctionally examined fibroblast populations in thecolon. CD90+ fibroblasts located in close proximityto stem cells in vivo support organoid growth in vitroand express crucial stem cell growth factors, suchas Grem1, Wnt2b, and R-spondin3. Moreover, wefound that CD90+ fibroblasts express a family ofproteins—class 3 semaphorins (Sema3)—that arerequired for the supportive effect of CD90+ fibroblastson organoid growth.