The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Stroma provides an intestinal stem cell niche in the absence of epithelial Wnts
Open accessAbstract
Wnt/β-catenin signaling supports intestinal homeostasis by regulating proliferation in the crypt. Multiple Wnts are expressed in Paneth cells as well as other intestinal epithelial and stromal cells. Ex vivo, Wnts secreted by Paneth cells can support intestinal stem cells when Wnt signaling is enhanced with supplemental R-Spondin 1 (RSPO1). However, in vivo, the source of Wnts in the stem cell niche is less clear. Genetic ablation of Porcn, an endoplasmic reticulum resident O-acyltransferase that is essential for the secretion and activity of all vertebrate Wnts, confirmed the role of intestinal epithelial Wnts in ex vivo culture. Unexpectedly, mice lacking epithelial Wnt activity (PorcnDel/Villin-Cre mice) had normal intestinal proliferation and differentiation, as well as successful regeneration after radiation injury, indicating that epithelial Wnts are dispensable for these processes. Consistent with a key role for stroma in the crypt niche, intestinal stromal cells endogenously expressing Wnts and Rspo3 support the growth of PorcnDel organoids ex vivo without RSPO1 supplementation. Conversely, increasing pharmacologic PORCN inhibition, affecting both stroma and epithelium, reduced Lgr5 intestinal stem cells, inhibited recovery from radiation injury, and at the highest dose fully blocked intestinal proliferation. We conclude that epithelial Wnts are dispensable and that stromal production of Wnts can fully support normal murine intestinal homeostasis.
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Cites
Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche
Sato, T., Vries, R. G., Snippert, H. J., van de Wetering, M., Barker, N., Stange, D. E., van Es, J. H., Abo, A., Kujala, P., Peters, P. J., et al. (2009) · Nature · doi:10.1038/nature07935 · Cited by 7,204
Identification of stem cells in small intestine and colon by marker gene Lgr5
Barker, N., van Es, J. H., Kuipers, J., Kujala, P., van den Born, M., Cozijnsen, M., Haegebarth, A., Korving, J., Begthel, H., Peters, P. J., et al. (2007) · Nature · doi:10.1038/nature06196 · Cited by 5,687
Wnt/β-catenin signaling and disease
Clevers, H., & Nusse, R. (2012) · Cell · doi:10.1016/j.cell.2012.05.012 · Cited by 5,554
Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts
Sato, T., van Es, J. H., Snippert, H. J., Stange, D. E., Vries, R. G., van den Born, M., Barker, N., Shroyer, N. F., van de Wetering, M., & Clevers, H. (2011) · Nature · doi:10.1038/nature09637 · Cited by 2,510
Intestinal label-retaining cells are secretory precursors expressing Lgr5
Buczacki, S. J. A., Zecchini, H. I., Nicholson, A. M., Russell, R., Vermeulen, L., Kemp, R., & Winton, D. J. (2013) · Nature · doi:10.1038/nature11965 · Cited by 761
Interconversion Between Intestinal Stem Cell Populations in Distinct Niches
Takeda, N., Jain, R., LeBoeuf, M. R., Wang, Q., Lu, M. M., & Epstein, J. A. (2011) · Science · doi:10.1126/science.1213214 · Cited by 742
Redundant sources of Wnt regulate intestinal stem cells and promote formation of Paneth cells
Farin, H. F., Van Es, J. H., & Clevers, H. (2012) · Gastroenterology · doi:10.1053/j.gastro.2012.08.031 · Cited by 655
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Lgr5 stem cells are indispensable for radiation-induced intestinal regeneration
Metcalfe, C., Kljavin, N. M., Ybarra, R., & de Sauvage, F. J. (2014) · Cell Stem Cell · doi:10.1016/j.stem.2013.11.008 · Cited by 575
Cited by
Wnt signaling in development and tissue homeostasis
Steinhart, Z., & Angers, S. (2018) · Development · doi:10.1242/dev.146589 · Cited by 821
Martini, E., Krug, S. M., Siegmund, B., Neurath, M. F., & Becker, C. (2017) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2017.03.007 · Cited by 668
Visualization of a short-range Wnt gradient in the intestinal stem-cell niche
Farin, H. F., Jordens, I., Mosa, M. H., Basak, O., Korving, J., Tauriello, D. V. F., de Punder, K., Angers, S., Peters, P. J., Maurice, M. M., et al. (2016) · Nature · doi:10.1038/nature16937 · Cited by 525
Microbiota-Derived Lactate Accelerates Intestinal Stem-Cell-Mediated Epithelial Development
Lee, Y.-S., Kim, T.-Y., Kim, Y., Lee, S.-H., Kim, S., Kang, S. W., Yang, J.-Y., Baek, I.-J., Sung, Y. H., Park, Y.-Y., et al. (2018) · Cell Host & Microbe · doi:10.1016/j.chom.2018.11.002 · Cited by 459
Non-equivalence of Wnt and R-spondin ligands during Lgr5+ intestinal stem-cell self-renewal
Yan, K. S., Janda, C. Y., Chang, J., Zheng, G. X. Y., Larkin, K. A., Luca, V. C., Chia, L. A., Mah, A. T., Han, A., Terry, J. M., et al. (2017) · Nature · doi:10.1038/nature22313 · Cited by 455
Metadata
- Authors
- Kabiri, Z., Greicius, G., Madan, B., Biechele, S., Zhong, Z., Zaribafzadeh, H., Edison, Aliyev, J., Wu, Y., Bunte, R., Williams, B. O., Rossant, J., & Virshup, D. M.
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2014-06-01
- Volume
- 141
- Issue
- 11
- Pages
- 2206-2215
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- OpenAlex
- W2168623286
- Cited by
- 338
- References
- 9
- FWCI
- 9.86
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Kabiri, Z., Greicius, G., Madan, B., Biechele, S., Zhong, Z., Zaribafzadeh, H., Edison, Aliyev, J., Wu, Y., Bunte, R., Williams, B. O., Rossant, J., & Virshup, D. M. (2014). Stroma provides an intestinal stem cell niche in the absence of epithelial Wnts. Development. https://doi.org/10.1242/dev.104976
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