Cargando…
Assessing Cellular and Transcriptional Diversity of Ileal Mucosa Among Treatment-Naïve and Treated Crohn’s Disease
BACKGROUND: Crohn’s disease is a lifelong disease characterized by chronic inflammation of the gastrointestinal tract. Defining the cellular and transcriptional composition of the mucosa at different stages of disease progression is needed for personalized therapy in Crohn’s. METHODS: Ileal biopsies...
Autores principales: | , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9890215/ https://www.ncbi.nlm.nih.gov/pubmed/36206201 http://dx.doi.org/10.1093/ibd/izac201 |
_version_ | 1784880904564375552 |
---|---|
author | Maddipatla, Sushma Chowdary Kolachala, Vasantha L Venkateswaran, Suresh Dodd, Anne F Pelia, Ranjit Singh Geem, Duke Yin, Hong Sun, Yutong Xu, Congmin Mo, Angela Kosters, Astrid Yang, Junkai Matthews, Jason D Ghosn, Eliver Kugathasan, Subra Qiu, Peng |
author_facet | Maddipatla, Sushma Chowdary Kolachala, Vasantha L Venkateswaran, Suresh Dodd, Anne F Pelia, Ranjit Singh Geem, Duke Yin, Hong Sun, Yutong Xu, Congmin Mo, Angela Kosters, Astrid Yang, Junkai Matthews, Jason D Ghosn, Eliver Kugathasan, Subra Qiu, Peng |
author_sort | Maddipatla, Sushma Chowdary |
collection | PubMed |
description | BACKGROUND: Crohn’s disease is a lifelong disease characterized by chronic inflammation of the gastrointestinal tract. Defining the cellular and transcriptional composition of the mucosa at different stages of disease progression is needed for personalized therapy in Crohn’s. METHODS: Ileal biopsies were obtained from (1) control subjects (n = 6), (2) treatment-naïve patients (n = 7), and (3) established (n = 14) Crohn’s patients along with remission (n = 3) and refractory (n = 11) treatment groups. The biopsies processed using 10x Genomics single cell 5' yielded 139 906 cells. Gene expression count matrices of all samples were analyzed by reciprocal principal component integration, followed by clustering analysis. Manual annotations of the clusters were performed using canonical gene markers. Cell type proportions, differential expression analysis, and gene ontology enrichment were carried out for each cell type. RESULTS: We identified 3 cellular compartments with 9 epithelial, 1 stromal, and 5 immune cell subtypes. We observed differences in the cellular composition between control, treatment-naïve, and established groups, with the significant changes in the epithelial subtypes of the treatment-naïve patients, including microfold, tuft, goblet, enterocyte,s and BEST4+ cells. Surprisingly, fewer changes in the composition of the immune compartment were observed; however, gene expression in the epithelial and immune compartment was different between Crohn’s phenotypes, indicating changes in cellular activity. CONCLUSIONS: Our study identified cellular and transcriptional signatures associated with treatment-naïve Crohn’s disease that collectively point to dysfunction of the intestinal barrier with an increase in inflammatory cellular activity. Our analysis also highlights the heterogeneity among patients within the same disease phenotype, shining a new light on personalized treatment responses and strategies. |
format | Online Article Text |
id | pubmed-9890215 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-98902152023-02-02 Assessing Cellular and Transcriptional Diversity of Ileal Mucosa Among Treatment-Naïve and Treated Crohn’s Disease Maddipatla, Sushma Chowdary Kolachala, Vasantha L Venkateswaran, Suresh Dodd, Anne F Pelia, Ranjit Singh Geem, Duke Yin, Hong Sun, Yutong Xu, Congmin Mo, Angela Kosters, Astrid Yang, Junkai Matthews, Jason D Ghosn, Eliver Kugathasan, Subra Qiu, Peng Inflamm Bowel Dis Basic Science Research BACKGROUND: Crohn’s disease is a lifelong disease characterized by chronic inflammation of the gastrointestinal tract. Defining the cellular and transcriptional composition of the mucosa at different stages of disease progression is needed for personalized therapy in Crohn’s. METHODS: Ileal biopsies were obtained from (1) control subjects (n = 6), (2) treatment-naïve patients (n = 7), and (3) established (n = 14) Crohn’s patients along with remission (n = 3) and refractory (n = 11) treatment groups. The biopsies processed using 10x Genomics single cell 5' yielded 139 906 cells. Gene expression count matrices of all samples were analyzed by reciprocal principal component integration, followed by clustering analysis. Manual annotations of the clusters were performed using canonical gene markers. Cell type proportions, differential expression analysis, and gene ontology enrichment were carried out for each cell type. RESULTS: We identified 3 cellular compartments with 9 epithelial, 1 stromal, and 5 immune cell subtypes. We observed differences in the cellular composition between control, treatment-naïve, and established groups, with the significant changes in the epithelial subtypes of the treatment-naïve patients, including microfold, tuft, goblet, enterocyte,s and BEST4+ cells. Surprisingly, fewer changes in the composition of the immune compartment were observed; however, gene expression in the epithelial and immune compartment was different between Crohn’s phenotypes, indicating changes in cellular activity. CONCLUSIONS: Our study identified cellular and transcriptional signatures associated with treatment-naïve Crohn’s disease that collectively point to dysfunction of the intestinal barrier with an increase in inflammatory cellular activity. Our analysis also highlights the heterogeneity among patients within the same disease phenotype, shining a new light on personalized treatment responses and strategies. Oxford University Press 2022-10-07 /pmc/articles/PMC9890215/ /pubmed/36206201 http://dx.doi.org/10.1093/ibd/izac201 Text en © 2022 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Basic Science Research Maddipatla, Sushma Chowdary Kolachala, Vasantha L Venkateswaran, Suresh Dodd, Anne F Pelia, Ranjit Singh Geem, Duke Yin, Hong Sun, Yutong Xu, Congmin Mo, Angela Kosters, Astrid Yang, Junkai Matthews, Jason D Ghosn, Eliver Kugathasan, Subra Qiu, Peng Assessing Cellular and Transcriptional Diversity of Ileal Mucosa Among Treatment-Naïve and Treated Crohn’s Disease |
title | Assessing Cellular and Transcriptional Diversity of Ileal Mucosa Among Treatment-Naïve and Treated Crohn’s Disease |
title_full | Assessing Cellular and Transcriptional Diversity of Ileal Mucosa Among Treatment-Naïve and Treated Crohn’s Disease |
title_fullStr | Assessing Cellular and Transcriptional Diversity of Ileal Mucosa Among Treatment-Naïve and Treated Crohn’s Disease |
title_full_unstemmed | Assessing Cellular and Transcriptional Diversity of Ileal Mucosa Among Treatment-Naïve and Treated Crohn’s Disease |
title_short | Assessing Cellular and Transcriptional Diversity of Ileal Mucosa Among Treatment-Naïve and Treated Crohn’s Disease |
title_sort | assessing cellular and transcriptional diversity of ileal mucosa among treatment-naïve and treated crohn’s disease |
topic | Basic Science Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9890215/ https://www.ncbi.nlm.nih.gov/pubmed/36206201 http://dx.doi.org/10.1093/ibd/izac201 |
work_keys_str_mv | AT maddipatlasushmachowdary assessingcellularandtranscriptionaldiversityofilealmucosaamongtreatmentnaiveandtreatedcrohnsdisease AT kolachalavasanthal assessingcellularandtranscriptionaldiversityofilealmucosaamongtreatmentnaiveandtreatedcrohnsdisease AT venkateswaransuresh assessingcellularandtranscriptionaldiversityofilealmucosaamongtreatmentnaiveandtreatedcrohnsdisease AT doddannef assessingcellularandtranscriptionaldiversityofilealmucosaamongtreatmentnaiveandtreatedcrohnsdisease AT peliaranjitsingh assessingcellularandtranscriptionaldiversityofilealmucosaamongtreatmentnaiveandtreatedcrohnsdisease AT geemduke assessingcellularandtranscriptionaldiversityofilealmucosaamongtreatmentnaiveandtreatedcrohnsdisease AT yinhong assessingcellularandtranscriptionaldiversityofilealmucosaamongtreatmentnaiveandtreatedcrohnsdisease AT sunyutong assessingcellularandtranscriptionaldiversityofilealmucosaamongtreatmentnaiveandtreatedcrohnsdisease AT xucongmin assessingcellularandtranscriptionaldiversityofilealmucosaamongtreatmentnaiveandtreatedcrohnsdisease AT moangela assessingcellularandtranscriptionaldiversityofilealmucosaamongtreatmentnaiveandtreatedcrohnsdisease AT kostersastrid assessingcellularandtranscriptionaldiversityofilealmucosaamongtreatmentnaiveandtreatedcrohnsdisease AT yangjunkai assessingcellularandtranscriptionaldiversityofilealmucosaamongtreatmentnaiveandtreatedcrohnsdisease AT matthewsjasond assessingcellularandtranscriptionaldiversityofilealmucosaamongtreatmentnaiveandtreatedcrohnsdisease AT ghosneliver assessingcellularandtranscriptionaldiversityofilealmucosaamongtreatmentnaiveandtreatedcrohnsdisease AT kugathasansubra assessingcellularandtranscriptionaldiversityofilealmucosaamongtreatmentnaiveandtreatedcrohnsdisease AT qiupeng assessingcellularandtranscriptionaldiversityofilealmucosaamongtreatmentnaiveandtreatedcrohnsdisease |