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. Display omitted •Spatial transcriptomics and 3D imaging reveal lymphatics as key crypt niche residents•SpaceFold maps cells and cell-specific transcriptomes to the intestinal crypt-villus axis•Lymphatics serve as a critical signaling hub in the intestinal stem cell niche•Lymphatic factors maintain epithelial stemness and restrict differentiation Niec et al. integrate spatial and single-cell transcriptomics data and develop computational approaches to finely map the cellular and transcriptional landscape of the intestinal crypt-villus axis. Combining these results with functional experiments, the authors expose lymphatics as a central signaling hub that promotes stem cell maintenance in the intestinal niche.