Dataset Information


ZIP7 is indispensable for proliferation of intestinal epithelial cells and maintenance of intestinal stem cells

ABSTRACT: Intestinal epithelium are generated by intestinal stem cells, which are recognized morphologically as slender columnar cells at the base of the crypt. Stem cells produce transit-amplifying (TA) cells, which divide a number of times and the daughter cells differentiate into absorptive enterocytes as well as secretory-lineages. Intestinal stem cells highly express Lgr5 which is decreased in TA cells. Here, we show that the zinc transported SLC39A7/ZIP7 is essential for the proliferation of TA cells and maintenance of intestinal stem cells. Lgr5Med TA cells derived from Zip7-deficient mice upregulated the expression of unfold protein responses-related genes including pro-apoptotic genes, indicating of induction of ER stress in these cells. The same effect was seen in Lgr5Hi stem cells derived from Zip7-deficient mice. We conclude that ZIP7 is fundamental to the maintenance of crypt homeostasis by resolving ER stress. Small intestinal crypts were isolated form tamoxifen-treated control (Zip7flox/+, Villin-CreERT2, Lgr5-EGFP-ires-CreERT2) and tamoxifen-treated Zip7∆IEC (Zip7flox/flox, Villin-CreERT2, Lgr5-EGFP-ires-CreERT2) mice. We FACS purified intestinal crypt cells according to their Lgr5 expression levels. RNA was isolated from four FACS sorted cell populations: Lgr5Hi cells and Lgr5Med cells derived from control mice, Lgr5Hi cells and Lgr5Med cells derived from Zip7∆IEC mice. Isolated RNA was analyzed using the Affymetrix platform.

ORGANISM(S): Mus musculus  

SUBMITTER: K Hase   W Ohashi  Yoshiki Mochizuki  T Fukada 

PROVIDER: E-GEOD-72190 | ArrayExpress | 2016-08-19



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