Casein kinase 1-epsilon or 1-delta required for Wnt-mediated intestinal stem cell maintenance.

Szczegóły
Abstrakt

Tytuł:: Casein kinase 1-epsilon or 1-delta required for Wnt-mediated intestinal stem cell maintenance.
Autorzy:: Morgenstern Y; The Lautenberg Center for Immunology, Institute of Medical Research, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Das Adhikari U; The Lautenberg Center for Immunology, Institute of Medical Research, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Ayyash M; The Lautenberg Center for Immunology, Institute of Medical Research, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Elyada E; The Lautenberg Center for Immunology, Institute of Medical Research, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Tóth B; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Moor A; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Itzkovitz S; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Ben-Neriah Y; The Lautenberg Center for Immunology, Institute of Medical Research, Hebrew University-Hadassah Medical School, Jerusalem, Israel .
Źródło:: The EMBO journal [EMBO J] 2017 Oct 16; Vol. 36 (20), pp. 3046-3061. Date of Electronic Publication: 2017 Sep 28.
Typ publikacji:: Journal Article
Język:: English
Imprint Name(s):: Publication: 2014- : London : Wiley Blackwell
Original Publication: Eynsham, Oxford, England : Published for the European Molecular Biology Organization by IRL Press, [c1982-
MeSH Terms:: Wnt Signaling Pathway*
Casein Kinase 1 epsilon/*metabolism
Casein Kinase Idelta/*metabolism
Intestinal Mucosa/*physiology
Stem Cells/*physiology
Animals ; Cell Proliferation ; Epithelial Cells/physiology ; Mice
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Contributed Indexing:: Keywords: LGR5; Wnt; adult stem cells; casein kinase I; intestine stem cells
Substance Nomenclature:: EC 2.7.11.1 (Casein Kinase 1 epsilon)
EC 2.7.11.1 (Casein Kinase Idelta)
Entry Date(s):: Date Created: 20171001 Date Completed: 20171020 Latest Revision: 20211204
Update Code:: 20240105
PubMed Central ID:: PMC5641904
DOI:: 10.15252/embj.201696253
PMID:: 28963394
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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.
(© 2017 The Authors.)

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