Lymphatics act as a signaling hub to regulate intestinal stem cell activity.
IF: 25.269
Cited by: 27


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.


Spatial Transcriptomics
intestinal stem cells
lymphatic:stem cell interactome
spatial deconvolution
spatial transcriptomics of murine large and small intestine
stem cell niches

MeSH terms

Cell Proliferation
Intestinal Mucosa
Signal Transduction
Stem Cells
Wnt Proteins


Niec, Rachel E
Chu, Tinyi
Schernthanner, Marina
Gur-Cohen, Shiri
Hidalgo, Lynette
Pasolli, Hilda Amalia
Luckett, Kathleen A
Wang, Zhong
Bhalla, Sohni R
Cambuli, Francesco
Kataru, Raghu P
Ganesh, Karuna
Mehrara, Babak J
Pe'er, Dana
Fuchs, Elaine

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