Beyaz, S., Roper, J., Bauer-Rowe, K. E., Xifaras, M. E., Ergin, I., Dohnalova, L., Biton, M., Shekar, K., Mou, H. W., Eskiocak, O., Ozata, D., Papciak, K., Chung, C., Almeqdadi, M., Fein, M., Valle-Encinas, E., Erdemir, A., Dogum, K, Garipcan, A., Meyer, H., Fox, J.G., Elinav, E., Kucukural, A., Kumar, P., McAleer, J., Thaiss, C.A., Regev, A., Orkin, S. H., Yilmaz, O. H. (September 2020) Dietary suppression of MHC-II expression in intestinal stem cells enhances intestinal tumorigenesis. bioRxiv. (Unpublished)
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Abstract
Little is known about how interactions between diet, immune recognition, and intestinal stem cells (ISCs) impact the early steps of intestinal tumorigenesis. Here, we show that a high fat diet (HFD) reduces the expression of the major histocompatibility complex II (MHC-II) genes in ISCs. This decline in ISC MHC-II expression in a HFD correlates with an altered intestinal microbiome composition and is recapitulated in antibiotic treated and germ-free mice on a control diet. Mechanistically, pattern recognition receptor and IFNg signaling regulate MHC-II expression in ISCs. Although MHC-II expression on ISCs is dispensable for stem cell function in organoid cultures in vitro, upon loss of the tumor suppressor gene Apc in a HFD, MHC-II- ISCs harbor greater in vivo tumor-initiating capacity than their MHC-II+ counterparts, thus implicating a role for epithelial MHC-II in suppressing tumorigenesis. Finally, ISC-specific genetic ablation of MHC-II in engineered Apc-mediated intestinal tumor models increases tumor burden in a cell autonomous manner. These findings highlight how a HFD alters the immune recognition properties of ISCs through the regulation of MHC-II expression in a manner that could contribute to intestinal tumorigenesis.
| Item Type: | Paper |
|---|---|
| Subjects: | Investigative techniques and equipment > cell culture > cancer organoids diseases & disorders > cancer > cancer types > intestinal cancer organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells |
| CSHL Authors: | |
| Communities: | CSHL labs > Beyaz lab CSHL labs > Meyer Lab School of Biological Sciences > Publications |
| Depositing User: | Sasha Luks-Morgan |
| Date: | 8 September 2020 |
| Date Deposited: | 08 Jun 2021 13:46 |
| Last Modified: | 29 Apr 2024 15:36 |
| URI: | https://repository.cshl.edu/id/eprint/40200 |
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