[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-362563-105":59,"doc-detail-362563-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","notch3-regulates-pericyte-phenotypic-plasticity-in-colorectal-cancer","Notch3 regulates pericyte phenotypic plasticity in colorectal cancer","","Notch3 regulates pericyte phenotypic plasticity in colorectal cancer by influencing both pericyte behavior and vascular outcomes. Lineage tracing shows tumor pericytes arise from resident normal-tissue pericytes that proliferate within tumors. In vivo genetic manipulation demonstrates that Notch3 activation increases pericyte proliferation while suppressing contractile protein expression, enhancing endothelial proliferation and reducing blood vessel integrity. Conversely, Notch3 deletion normalizes vessels, lowers endothelial proliferation, and significantly reduces tumorigenesis in an advanced orthotopic mouse model. Single-cell RNA-seq reveals pericyte heterogeneity with distinct Notch3-activity subpopulations linked to tumor states.",{"@graph":69,"@context":122},[70,84,105],{"@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":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/notch3-regulates-pericyte-phenotypic-plasticity-in-colorectal-cancer/362563/",{"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/notch3-regulates-pericyte-phenotypic-plasticity-in-colorectal-cancer/362563.png","ImageObject",300,407,{"name":92,"@type":93},"Maya Linwood","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-28","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":19},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"How does Notch3 activation affect pericyte phenotype in colorectal cancer?","Question",{"text":112,"@type":113},"Notch3 activation promotes pericyte proliferation while suppressing contractile protein expression, shifting pericytes toward a less contractile phenotype.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What is the effect of deleting Notch3 in vivo on tumor vasculature?",{"text":117,"@type":113},"Notch3 deletion decreases endothelial proliferation, normalizes blood vessels, and significantly reduces tumorigenesis in an advanced orthotopic mouse model.",{"name":119,"@type":110,"acceptedAnswer":120},"What does single-cell RNA sequencing reveal about pericytes?",{"text":121,"@type":113},"Single-cell RNA sequencing uncovers pericyte heterogeneity in both mouse colitis-associated cancer and human colorectal cancer, identifying distinct subpopulations with differential Notch3 activity.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},362563,1790323286,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":19,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},962084928432,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","communications biology Article  \nA Nature Portfolio journal  \n[https://doi.org/10.1038/s42003-026-09629-4](https://doi.org/10.1038/s42003-026-09629-4)  \nNotch3 regulates pericyte phenotypic plasticity in colorectal cancer  \n Check for updates  \n\n| Niki Chalkidi1,4, Athanasia Stavropoulou1,2,4, Vasiliki-Zoi Arvaniti1, Christina Paraskeva1, Artemis Monogyiou1, Maria Sakkou2,3, Christoforos Nikolaou2 & Vasiliki Koliaraki 1  |  |\n| --- | --- |\n| Pericytes, essential components of the tumor microenvironment, undergo phenotypic alterations that influence cancer progression, yet the molecular mechanisms governing these changes remain poorly understood. Here, we investigate the role of Notch3 signaling in pericyte phenotype and functions in colorectal cancer (CRC) . Using lineage tracing approaches, we show that murine tumor pericytes originate from normal tissue-resident pericytes, which proliferate inside tumors. In vivo genetic manipulation reveals that Notch3 pathway activation promotes pericyte proliferation, while suppressing contractile protein expression, and leads to increased endothelial cell proliferation and reduced blood vessel integrity. In contrast, Notch3 deletion leads to decreased endothelial proliferation, blood vessel normalization, and a significant reduction in tumorigenesis in an advanced orthotopic mouse model. Single-cell RNA sequencing analysis uncovers significant pericyte heterogeneity in both mouse colitis-associated cancer and human CRC. It specifically identifies distinct subpopulations characterized by differential Notch3 activity, which is enriched in a synthetic subset and absent in a contractile subset, further supporting our in vivo findings. Our results establish Notch3 as a key regulator of pericyte phenotypic plasticity in CRC and suggest that targeting this pathway could represent a promising strategy for improving therapeutic outcomes through vascular normalization. |  |\n| Colorectal cancer(CRC)remains asignificant global health burden, ranking as the third most diagnosed cancer and the second leading cause of cancerrelated mortality worldwide1,2. This highlights the need for new therapeutic approaches based on a deeper understanding of CRC biology. Recent research has uncovered the crucial role of the tumor microenvironment (TME) in CRC progression, metastasis, and therapy resistance3,4. The TME consists of diverse cell populations, including fibroblasts, immune cells, endothelial cells, and pericytes, which collectively influence tumor behavior through complex intercellular communications and extracellular matrix remodeling4. Notably, both cancer cells and componentsoftheTME exhibit remarkable plasticity, enabling them to transition to distinct cell states with tumor-promoting phenotypic and functional properties5.\u003Cbr>Pericytes are specialized perivascular cells embedded within the basement membrane of microvessels, where they establish direct physical contact with endothelial cells6. In physiological conditions, pericytes play essential roles in vascular development, stabilization, and maturation by regulating endothelial cell proliferation, vessel diameter, and basement membrane deposition. The recruitment and differentiation of pericytes | along nascent vessels are tightly regulated by several signaling pathways, such as PDGF-B, TGFβ, and angiopoietin. Disruption of these pathways leads to pericyte deficiency, vascular instability, and subsequent pathologies, emphasizing the importance of proper pericyte function in vascular homeostasis6. In cancer, pericytes undergo significant alterations in their phenotype, distribution, and functionality, contributing to tumor angiogenesis by regulating vascular integrity, permeability, and remodeling7. Tumor vessels typically exhibit abnormal pericyte coverage characterizedby loose attachment to endothelial cells, cytoplasmic processes extending into the tumor parenchyma, and altered expression of marker proteins. These abnormalities contribute to vessel leakine","cbCaio9czlcyNF8D","https://ap.wps.com/l/cbCaio9czlcyNF8D","pdf",4303257,14,"English","# Introduction\n## Tumor microenvironment and pericyte plasticity\n## Notch signaling and study rationale\n# Results\n## Lineage tracing and pericyte origin\n## Genetic manipulation of Notch3 signaling","[{\"question\":\"How does Notch3 activation affect pericyte phenotype in colorectal cancer?\",\"answer\":\"Notch3 activation promotes pericyte proliferation while suppressing contractile protein expression, shifting pericytes toward a less contractile phenotype.\"},{\"question\":\"What is the effect of deleting Notch3 in vivo on tumor vasculature?\",\"answer\":\"Notch3 deletion decreases endothelial proliferation, normalizes blood vessels, and significantly reduces tumorigenesis in an advanced orthotopic mouse model.\"},{\"question\":\"What does single-cell RNA sequencing reveal about pericytes?\",\"answer\":\"Single-cell RNA sequencing uncovers pericyte heterogeneity in both mouse colitis-associated cancer and human colorectal cancer, identifying distinct subpopulations with differential Notch3 activity.\"}]","Notch3 regulates pericyte phenotypic plasticity in colorectal cancer | PDF",1790148271,35]