Lymphatics act as a signaling hub to regulate intestinal stem cell activity Journal Article

   


Authors: Niec, R. E.; Chu, T.; Schernthanner, M.; Gur-Cohen, S.; Hidalgo, L.; Pasolli, H. A.; Luckett, K. A.; Wang, Z.; Bhalla, S. R.; Cambuli, F.; Kataru, R. P.; Ganesh, K.; Mehrara, B. J.; Pe'er, D.; Fuchs, E.
Article Title: Lymphatics act as a signaling hub to regulate intestinal stem cell activity
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. © 2022 Elsevier Inc.
Keywords: signal transduction; cell proliferation; metabolism; stem cell; stem cells; wnt proteins; wnt protein; intestine; intestines; intestine mucosa; intestinal mucosa; lymphatics; reelin; organoids; wnts; organoid; intestinal stem cells; lymphatic:stem cell interactome; rspo3; spatial deconvolution; spatial transcriptomics of murine large and small intestine; stem cell niches
Journal Title: Cell Stem Cell
Volume: 29
Issue: 7
ISSN: 1934-5909
Publisher: Cell Press  
Date Published: 2022-07-07
Start Page: 1067
End Page: 1082.e18
Language: English
DOI: 10.1016/j.stem.2022.05.007
PUBMED: 35728595
PROVIDER: scopus
PMCID: PMC9271639
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85133488692&doi=10.1016%2fj.stem.2022.05.007&partnerID=40&md5=a1b4614ea4afe052bd568ad2f1a8626a
Notes: Article -- Export Date: 1 August 2022 -- Source: Scopus
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MSK Authors
  1. Babak Mehrara
    448 Mehrara
  2. Karuna Ganesh
    68 Ganesh
  3. Raghu Prasad Kataru
    60 Kataru
  4. Dana Pe'er
    110 Pe'er
  5. Kathleen A Luckett
    6 Luckett
  6. Francesco Cambuli
    4 Cambuli
  7. Tin Yi Chu
    7 Chu
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