Abstract：
:The gut absorbs dietary nutrients and provides a barrier to xenobiotics and microbiome metabolites. To cope with toxin exposures, the intestinal epithelium is one of the most rapidly proliferating tissues in the body. The stem cell niche supplies essential signaling factors including Wnt proteins secreted by subepithelial myofibroblasts. Unexpectedly, therapeutically effective doses of orally administered PORCN inhibitors that block all Wnt secretion do not affect intestinal homeostasis. We find that intestinal myofibroblasts are intrinsically resistant to multiple xenobiotics, including PORCN inhibitors and the anthracycline antibiotic doxorubicin. These myofibroblasts have high expression of a subset of drug transporters; knockout of Mrp1/Abcc1 enhances drug sensitivity. Tamoxifen administration to Rosa26CreERT2;mT/mG mice visually highlights the drug-resistant intestinal stromal compartment and identifies small populations of drug-resistant cells in lung, kidney, and pancreatic islets. Xenobiotic resistance of the Wnt-producing myofibroblasts can protect the intestinal stem cell niche in the face of an unpredictable environment.
journal_name
Dev Celljournal_title
Developmental cellauthors
Chee YC,Pahnke J,Bunte R,Adsool VA,Madan B,Virshup DMdoi
10.1016/j.devcel.2018.07.023subject
Has Abstractpub_date
2018-09-24 00:00:00pages
681-695.e5issue
6eissn
1534-5807issn
1878-1551pii
S1534-5807(18)30608-7journal_volume
46pub_type
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journal_title：Developmental cell
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