Altered inflammatory mucosal signatures within their spatial and cellular context during active ileal Crohn's disease.

IF 6.3 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Vasantha L Kolachala, Sushma Chowdary Maddipatla, Shanta Murthy, Yeonjoo Hwang, Anne F Dodd, Garima Sharma, Sachith Munasinghe, Ranjit Singh Pelia, Suresh Venkateswaran, Murugadas Anbazhagan, Tarun Koti, Navdeep Jhita, Gaurav N Joshi, Chrissy A Lopez, Duke Geem, Hong Yin, David J Cutler, Peng Qiu, Jason D Matthews, Subra Kugathasan
{"title":"Altered inflammatory mucosal signatures within their spatial and cellular context during active ileal Crohn's disease.","authors":"Vasantha L Kolachala, Sushma Chowdary Maddipatla, Shanta Murthy, Yeonjoo Hwang, Anne F Dodd, Garima Sharma, Sachith Munasinghe, Ranjit Singh Pelia, Suresh Venkateswaran, Murugadas Anbazhagan, Tarun Koti, Navdeep Jhita, Gaurav N Joshi, Chrissy A Lopez, Duke Geem, Hong Yin, David J Cutler, Peng Qiu, Jason D Matthews, Subra Kugathasan","doi":"10.1172/jci.insight.171783","DOIUrl":null,"url":null,"abstract":"<p><p>Crohn's disease (CD) involves a complex intestinal microenvironment driven by chronic inflammation. While single-cell RNA sequencing has provided valuable insights into this biology, the spatial context is lost during single-cell preparation of mucosal biopsies. To deepen our understanding of the distinct inflammatory signatures of CD and overcome the limitations of single-cell RNA sequencing, we combined spatial transcriptomics of frozen CD surgical tissue sections with single-cell transcriptomics of ileal CD mucosa. Coexpressed genes and cell-cell communication from single-cell analyses and factorized genes from spatial transcriptomics revealed overlapping pathways affected in inflamed CD, like antigen presentation, phagosome activity, cell adhesion, and extracellular matrix. Within the pathways, early epithelial cells showed evidence of significant changes in gene expression and subtype composition, while spatial mapping revealed the location of the events, particularly antigen presentation from epithelial cells in the base of the crypt. Furthermore, we identified early epithelial cells as a potential mediator of the MHC class II pathway during inflammation, which we validated by spatial transcriptomics cell subtype deconvolution. Therefore, the inflammation from CD appears to change the types of interactions detectable between epithelial cells with immune and mesenchymal cells, likely promoting the conditions for more macrophage infiltration into these inflammatory microdomains.</p>","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":"10 5","pages":""},"PeriodicalIF":6.3000,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"JCI insight","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1172/jci.insight.171783","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0

Abstract

Crohn's disease (CD) involves a complex intestinal microenvironment driven by chronic inflammation. While single-cell RNA sequencing has provided valuable insights into this biology, the spatial context is lost during single-cell preparation of mucosal biopsies. To deepen our understanding of the distinct inflammatory signatures of CD and overcome the limitations of single-cell RNA sequencing, we combined spatial transcriptomics of frozen CD surgical tissue sections with single-cell transcriptomics of ileal CD mucosa. Coexpressed genes and cell-cell communication from single-cell analyses and factorized genes from spatial transcriptomics revealed overlapping pathways affected in inflamed CD, like antigen presentation, phagosome activity, cell adhesion, and extracellular matrix. Within the pathways, early epithelial cells showed evidence of significant changes in gene expression and subtype composition, while spatial mapping revealed the location of the events, particularly antigen presentation from epithelial cells in the base of the crypt. Furthermore, we identified early epithelial cells as a potential mediator of the MHC class II pathway during inflammation, which we validated by spatial transcriptomics cell subtype deconvolution. Therefore, the inflammation from CD appears to change the types of interactions detectable between epithelial cells with immune and mesenchymal cells, likely promoting the conditions for more macrophage infiltration into these inflammatory microdomains.

求助全文
约1分钟内获得全文 求助全文
来源期刊
JCI insight
JCI insight Medicine-General Medicine
CiteScore
13.70
自引率
1.20%
发文量
543
审稿时长
6 weeks
期刊介绍: JCI Insight is a Gold Open Access journal with a 2022 Impact Factor of 8.0. It publishes high-quality studies in various biomedical specialties, such as autoimmunity, gastroenterology, immunology, metabolism, nephrology, neuroscience, oncology, pulmonology, and vascular biology. The journal focuses on clinically relevant basic and translational research that contributes to the understanding of disease biology and treatment. JCI Insight is self-published by the American Society for Clinical Investigation (ASCI), a nonprofit honor organization of physician-scientists founded in 1908, and it helps fulfill the ASCI's mission to advance medical science through the publication of clinically relevant research reports.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信