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Casein kinase 1‐epsilon or 1‐delta required for Wnt‐mediated intestinal stem cell maintenance
Author(s) -
Morgenstern Yael,
Das Adhikari Upasana,
Ayyash Muneef,
Elyada Ela,
Tóth Beáta,
Moor Andreas,
Itzkovitz Shalev,
BenNeriah Yi
Publication year - 2017
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201696253
Subject(s) - hebrew , medical school , library science , research center , medicine , classics , history , medical education , computer science , pathology
The intestinal epithelium holds an immense regenerative capacity mobilized by intestinal stem cells ( ISC s), much of it supported by Wnt pathway activation. Several unique regulatory mechanisms ensuring optimal levels of Wnt signaling have been recognized in ISC s. Here, we identify another Wnt signaling amplifier, CKI ε, which is specifically upregulated in ISC s and is essential for ISC maintenance, especially in the absence of its close isoform CKI δ. Co‐ablation of CKI δ/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 CKI δ/ε‐deficient enterocyte populations, with the exception of Lgr5 + ISC s, which exhibit Dvl2‐dependent Wnt signaling attenuation. CKI δ/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 ISC s, possibly providing new means of stem cell enrichment for regenerative medicine.