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Immortalized human colonic epithelial cells are exposed to a chronic inflammation mimic or to chemical peroxide, and adaptation responses are assessed in vitro and validated using biological databases. The findings show a partial genetic reprogramming that recurs in Crohn’s and ulcerative colitis mucosae as disease progresses. Activation is further confirmed in intestinal precursor cells during murine colorectal cancer development, linking adaptive programs to progression and possible tumor initiation.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/intestinal-epithelial-cells-adapt-to-chronic-inflammation-through-partial-genetic-reprogramming/380857/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/intestinal-epithelial-cells-adapt-to-chronic-inflammation-through-partial-genetic-reprogramming/380857.png","ImageObject",300,407,{"name":92,"@type":93},"hdkawk","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-27","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What role do ROS play in inflammatory bowel disease and this study?","Question",{"text":113,"@type":114},"ROS are described as major drivers of inflammatory bowel disease, and the study tests whether persistent ROS exposure pushes intestinal stem cells to activate protective strategies.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How did the researchers model chronic inflammation in intestinal epithelial cells?",{"text":118,"@type":114},"The study exposed immortalized human colonic epithelial cells to either a mimic of chronic inflammation or a chemical peroxide and then analyzed how cells adapted to oxidative stress.",{"name":120,"@type":111,"acceptedAnswer":121},"What is the key adaptation mechanism reported in the results?",{"text":122,"@type":114},"Cells adapt to chronic-inflammation-associated oxidative stress in vitro through a partial genetic reprogramming, which is recurrently active in patient mucosae and present in murine intestinal precursor cells during colorectal cancer development.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},380857,1790320988,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146},3985747859855,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","cancers   \nArticle  \nIntestinal Epithelial Cells Adapt to Chronic Inflammation through Partial Genetic Reprogramming  \nGuillaume Collin 1, Jean-Philippe Foy 1, Nicolas Aznar 1, Nicolas Rama 1, Anne Wierinckx 2, Pierre Saintigny 3, Alain Puisieux 1 and St²phane Ansieau 1, *  \nCitation: Collin, G.; Foy, J.-P.; Aznar, N.; Rama, N.; Wierinckx, A.;  \nSaintigny, P.; Puisieux, A.; Ansieau, S. Intestinal Epithelial Cells Adapt to Chronic Inflammation through Partial Genetic Reprogramming. Cancers 2023, 15, 973. [https://](https://)[ ](https://)[doi.org/10.3390/cancers15030973](doi.org/10.3390/cancers15030973)  \nAcademic Editor: Alain P. Gobert  \nReceived: 12 January 2023  \nRevised: 30 January 2023  \nAccepted: 1 February 2023  \nPublished: 3 February 2023  \nCopyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Centre de Recherche en Canc²rologie de Lyon, INSERM U1052, CNRS UMR 5286, Centre L²on B²rard, Universit² Lyon1, 69008 Lyon, France  \n2 ProfileXpert, 69008 Lyon, France  \n3 Department of Medical Oncology, Centre L²on B²rard, 69008 Lyon, France  \n* Correspondence: [stephane.ansieau@lyon.unicancer.fr](stephane.ansieau@lyon.unicancer.fr); Tel.: +33-(0)469-166-680  \nSimple Summary: Chronic inflammation, as observed in Crohn's disease and ulcerative colitis patients, damages the intestinal mucosa. We reasoned that if a subset of intestinal epithelial cells adapt to this inflammatory stress to survive, this adaptation could contribute to their malignant transformation. We show that human colonic epithelial cells escape chronic inflammation in vitro through a partial genetic reprogramming. By questioning data bases, we confirm that this reprogramming takes place in the inflamed mucosae of patients with Crohn's disease and ulcerative colitis, and that it is induced in vivo during the early stages of murine intestinal carcinogenesis. These data contribute to understanding the pathology and underline how orchestrators of cellular adaptation might contribute to intestinal homeostasis and, potentially, tumor initiation.  \nAbstract: Reactive oxygen species (ROS) are considered tobe the main drivers of inflammatory bowel disease. We investigated whether this permanent insult compels intestinal stem cells to develop strategies to dampen the deleterious effects of ROS. As an adverse effect, this adaptation process may increase their tolerance to oncogenic insults and facilitate their neoplastic transformation. We submitted immortalized human colonic epithelial cells to either a mimic of chronic inflammation or toa chemical peroxide, analyzed how they adapted to stress, and addressed the biological relevance of these observations in databases. We demonstrated that cells adapt to chronic-inflammation-associated oxidative stress in vitro through a partial genetic reprogramming. Through a gene set enrichment analysis, we showed that this program is recurrently active in the intestinal mucosae of Crohn's and ulcerative colitis disease patients and evolves alongside disease progression. Based on a previously reported characterization of intestinal stem and precursor cells using tracing experiments, we lastly confirmed the activation of the program in intestinal precursor cells during murine colorectal cancer development. This adaptive process is thus likely to play a role in the progression of Crohn's and ulcerative disease, and potentially in the initiation of colorectal cancer.  \nKeywords: adaptation to chronic-inflammation-associated oxidative stress; intestinal cell reprogramming; ZEB transcription factors; inflammatory bowel disease progression  \n1. Introduction  \nChronic inflammation of the intestinal epithelium, observed in patients with inflammatory bowel d","cbCaigTpRTDxa2dq","https://ap.wps.com/l/cbCaigTpRTDxa2dq","pdf",7018286,17,"English","# Simple Summary\n# Abstract\n# Keywords\n# 1. Introduction","[{\"question\":\"What role do ROS play in inflammatory bowel disease and this study?\",\"answer\":\"ROS are described as major drivers of inflammatory bowel disease, and the study tests whether persistent ROS exposure pushes intestinal stem cells to activate protective strategies.\"},{\"question\":\"How did the researchers model chronic inflammation in intestinal epithelial cells?\",\"answer\":\"The study exposed immortalized human colonic epithelial cells to either a mimic of chronic inflammation or a chemical peroxide and then analyzed how cells adapted to oxidative stress.\"},{\"question\":\"What is the key adaptation mechanism reported in the results?\",\"answer\":\"Cells adapt to chronic-inflammation-associated oxidative stress in vitro through a partial genetic reprogramming, which is recurrently active in patient mucosae and present in murine intestinal precursor cells during colorectal cancer development.\"}]","Intestinal Epithelial Cells Adapt to Chronic Inflammation through Partial Genetic Reprogramming | PDF",1790242437,43]