Lymphatics act as a signaling hub to regulate intestinal stem cell activity.
| Publication Type | Academic Article |
| Authors | Niec R, Chu T, Schernthanner M, Gur-Cohen S, Hidalgo L, Pasolli H, Luckett K, Wang Z, Bhalla S, Cambuli F, Kataru R, Ganesh K, Mehrara B, Pe'er D, Fuchs E |
| Journal | Cell Stem Cell |
| Volume | 29 |
| Issue | 7 |
| Pagination | 1067-1082.e18 |
| Date Published | 06/20/2022 |
| ISSN | 1875-9777 |
| Keywords | Intestines, Stem Cells |
| Abstract | Barrier epithelia depend upon resident stem cells for homeostasis, defense, and repair. Epithelial stem cells of small and large intestines (ISCs) respond to their local microenvironments (niches) to fulfill a continuous demand for tissue turnover. The complexity of these niches and underlying communication pathways are not fully known. Here, we report a lymphatic network at the intestinal crypt base that intimately associates with ISCs. Employing in vivo loss of function and lymphatic:organoid cocultures, we show that crypt lymphatics maintain ISCs and inhibit their precocious differentiation. Pairing single-cell and spatial transcriptomics, we apply BayesPrism to deconvolve expression within spatial features and develop SpaceFold to robustly map the niche at high resolution, exposing lymphatics as a central signaling hub for the crypt in general and ISCs in particular. We identify WNT-signaling factors (WNT2, R-SPONDIN-3) and a hitherto unappreciated extracellular matrix protein, REELIN, as crypt lymphatic signals that directly govern the regenerative potential of ISCs. |
| DOI | 10.1016/j.stem.2022.05.007 |
| PubMed ID | 35728595 |
| PubMed Central ID | PMC9271639 |