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Casein kinase 1-epsilonor1-delta required for Wnt-mediated intestinal stem cell maintenance

Item Type:Article
Title:Casein kinase 1-epsilonor1-delta required for Wnt-mediated intestinal stem cell maintenance
Creators Name:Morgenstern, Y. and Das Adhikari, U. and Ayyash, M. and Elyada, E. and Tóth, B. and Moor, A. and Itzkovitz, S. and Ben-Neriah, Y.
Abstract:The intestinal epithelium holds an immense regenerative capacity mobilized by intestinal stem cells (ISCs), much of it supported by Wnt pathway activation. Several unique regulatory mechanisms ensuring optimal levels of Wnt signaling have been recognized in ISCs. Here, we identify another Wnt signaling amplifier, CKIε, which is specifically upregulated in ISCs and is essential for ISC maintenance, especially in the absence of its close isoform CKIδ. Co-ablation of CKIδ/ε in the mouse gut epithelium results in rapid ISC elimination, with subsequent growth arrest, crypt-villous shrinking, and rapid mouse death. Unexpectedly, Wnt activation is preserved in all CKIδ/ε-deficient enterocyte populations, with the exception of Lgr5(+) ISCs, which exhibit Dvl2-dependent Wnt signaling attenuation. CKIδ/ε-depleted gut organoids cease proliferating and die rapidly, yet survive and resume self-renewal upon reconstitution of Dvl2 expression. Our study underscores a unique regulation mode of the Wnt pathway in ISCs, possibly providing new means of stem cell enrichment for regenerative medicine.
Keywords:Adult Stem Cells, Casein Kinase I, Intestine Stem Cells, LGR5, Wnt, Animals, Mice
Source:EMBO Journal
ISSN:0261-4189
Publisher:EMBO Press
Volume:36
Number:20
Page Range:3046-3061
Date:16 October 2017
Official Publication:https://doi.org/10.15252/embj.201696253
PubMed:View item in PubMed

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