@article{zwarycz_gracz_rivera_williamson_samsa_starmer_daniele_salter-cid_zhao_magness_2019, title={IL22 Inhibits Epithelial Stem Cell Expansion in an Ileal Organoid Model}, volume={7}, ISSN={["2352-345X"]}, DOI={10.1016/j.jcmgh.2018.06.008}, abstractNote={Crohn's disease is an inflammatory bowel disease that affects the ileum and is associated with increased cytokines. Although interleukin (IL)6, IL17, IL21, and IL22 are increased in Crohn's disease and are associated with disrupted epithelial regeneration, little is known about their effects on the intestinal stem cells (ISCs) that mediate tissue repair. We hypothesized that ILs may target ISCs and reduce ISC-driven epithelial renewal.A screen of IL6, IL17, IL21, or IL22 was performed on ileal mouse organoids. Computational modeling was used to predict microenvironment cytokine concentrations. Organoid size, survival, proliferation, and differentiation were characterized by morphometrics, quantitative reverse-transcription polymerase chain reaction, and immunostaining on whole organoids or isolated ISCs. ISC function was assayed using serial passaging to single cells followed by organoid quantification. Single-cell RNA sequencing was used to assess Il22ra1 expression patterns in ISCs and transit-amplifying (TA) progenitors. An IL22-transgenic mouse was used to confirm the impact of increased IL22 on proliferative cells in vivo.High IL22 levels caused decreased ileal organoid survival, however, resistant organoids grew larger and showed increased proliferation over controls. Il22ra1 was expressed on only a subset of ISCs and TA progenitors. IL22-treated ISCs did not show appreciable differentiation defects, but ISC biomarker expression and self-renewal-associated pathway activity was reduced and accompanied by an inhibition of ISC expansion. In vivo, chronically increased IL22 levels, similar to predicted microenvironment levels, showed increases in proliferative cells in the TA zone with no increase in ISCs.Increased IL22 limits ISC expansion in favor of increased TA progenitor cell expansion.}, number={1}, journal={CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY}, author={Zwarycz, Bailey and Gracz, Adam D. and Rivera, Kristina R. and Williamson, Ian A. and Samsa, Leigh A. and Starmer, Josh and Daniele, Michael A. and Salter-Cid, Luisa and Zhao, Qihong and Magness, Scott T.}, year={2019}, pages={1–17} }
 @article{wang_disalvo_gunasekara_dutton_proctor_lebhar_williamson_speer_howard_smiddy_et al._2017, title={Self-renewing monolayer of primary colonic or rectal epithelial cells}, volume={4}, number={1}, journal={Cellular and Molecular Gastroenterology and Hepatology}, author={Wang, Y. L. and DiSalvo, M. and Gunasekara, D. B. and Dutton, J. and Proctor, A. and Lebhar, M. S. and Williamson, I. A. and Speer, J. and Howard, R. L. and Smiddy, N. M. and et al.}, year={2017}, pages={165-} }
 @article{attayek_ahmad_wang_williamson_sims_magness_allbritton_2016, title={In vitro polarization of colonoids to create an intestinal stem cell compartment}, volume={11}, number={4}, journal={PLoS One}, author={Attayek, P. J. and Ahmad, A. A. and Wang, Y. L. and Williamson, I. and Sims, C. E. and Magness, S. T. and Allbritton, N. L.}, year={2016} }