Digital Spatial Profiling Reveals Functional Shift of Enterochromaffin Cell in Patients With Ulcerative Colitis
As a major component of the enteroendocrine system, enterochromaffin (EC) cells play a key role in ulcerative colitis (UC). However, the scarcity of EC cells has limited the investigation of their function. In this study, we applied digital spatial profiling to acquire transcriptomic data for EC cel...
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Frontiers Media S.A.
2022-04-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2022.841090/full |
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author | Dongping Lyu Dongping Lyu Guanjun Kou Guanjun Kou Shiyang Li Shiyang Li Shiyang Li Lixiang Li Lixiang Li Lixiang Li Bing Li Bing Li Ruchen Zhou Ruchen Zhou Xiaoxiao Yang Xiaoxiao Yang Wenyu Tian Yanqing Li Yanqing Li Yanqing Li Xiuli Zuo Xiuli Zuo Xiuli Zuo |
author_facet | Dongping Lyu Dongping Lyu Guanjun Kou Guanjun Kou Shiyang Li Shiyang Li Shiyang Li Lixiang Li Lixiang Li Lixiang Li Bing Li Bing Li Ruchen Zhou Ruchen Zhou Xiaoxiao Yang Xiaoxiao Yang Wenyu Tian Yanqing Li Yanqing Li Yanqing Li Xiuli Zuo Xiuli Zuo Xiuli Zuo |
author_sort | Dongping Lyu |
collection | DOAJ |
description | As a major component of the enteroendocrine system, enterochromaffin (EC) cells play a key role in ulcerative colitis (UC). However, the scarcity of EC cells has limited the investigation of their function. In this study, we applied digital spatial profiling to acquire transcriptomic data for EC cells and other epithelial cells from colonoscopic biopsy samples from eight patients with UC and seven healthy controls. Differential expression analysis, gene set enrichment analysis, and weighted gene coexpression network analysis were performed to identify differentially expressed genes and pathways and coexpression networks. Results were validated using an online dataset obtained by single-cell RNA sequencing, along with immunofluorescence staining and quantitative real-time PCR. In healthy participants, 10 genes were significantly enriched in EC cells, functionally concentrated in protein and bioamine synthesis. A coexpression network containing 17 hub genes, including TPH1, CHGA, and GCLC, was identified in EC cells. In patients with UC, EC cells gained increased capacity for protein synthesis, along with novel immunological functions such as antigen processing and presentation, whereas chemical sensation was downregulated. The specific expression of CHGB and RGS2 in EC cells was confirmed by immunofluorescence staining. Our results illuminate the transcriptional signatures of EC cells in the human colon. EC cells’ newly observed functional shift from sensation to secretion and immunity indicates their pivotal role in UC. |
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spelling | doaj.art-550dfa591d764b3a8e843738c393556d2022-12-21T23:28:15ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-04-011010.3389/fcell.2022.841090841090Digital Spatial Profiling Reveals Functional Shift of Enterochromaffin Cell in Patients With Ulcerative ColitisDongping Lyu0Dongping Lyu1Guanjun Kou2Guanjun Kou3Shiyang Li4Shiyang Li5Shiyang Li6Lixiang Li7Lixiang Li8Lixiang Li9Bing Li10Bing Li11Ruchen Zhou12Ruchen Zhou13Xiaoxiao Yang14Xiaoxiao Yang15Wenyu Tian16Yanqing Li17Yanqing Li18Yanqing Li19Xiuli Zuo20Xiuli Zuo21Xiuli Zuo22Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, ChinaLaboratory of Translational Gastroenterology, Qilu Hospital, Shandong University, Jinan, ChinaDepartment of Gastroenterology, Qilu Hospital, Shandong University, Jinan, ChinaLaboratory of Translational Gastroenterology, Qilu Hospital, Shandong University, Jinan, ChinaDepartment of Gastroenterology, Qilu Hospital, Shandong University, Jinan, ChinaAdvanced Medical Research Institute, Shandong University, Jinan, ChinaKey Laboratory for Experimental Teratology of Ministry of Education, Shandong University, Jinan, ChinaDepartment of Gastroenterology, Qilu Hospital, Shandong University, Jinan, ChinaLaboratory of Translational Gastroenterology, Qilu Hospital, Shandong University, Jinan, ChinaRobot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital, Shandong University, Jinan, ChinaDepartment of Gastroenterology, Qilu Hospital, Shandong University, Jinan, ChinaLaboratory of Translational Gastroenterology, Qilu Hospital, Shandong University, Jinan, ChinaDepartment of Gastroenterology, Qilu Hospital, Shandong University, Jinan, ChinaLaboratory of Translational Gastroenterology, Qilu Hospital, Shandong University, Jinan, ChinaDepartment of Gastroenterology, Qilu Hospital, Shandong University, Jinan, ChinaLaboratory of Translational Gastroenterology, Qilu Hospital, Shandong University, Jinan, ChinaAdvanced Medical Research Institute, Shandong University, Jinan, ChinaDepartment of Gastroenterology, Qilu Hospital, Shandong University, Jinan, ChinaLaboratory of Translational Gastroenterology, Qilu Hospital, Shandong University, Jinan, ChinaRobot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital, Shandong University, Jinan, ChinaDepartment of Gastroenterology, Qilu Hospital, Shandong University, Jinan, ChinaLaboratory of Translational Gastroenterology, Qilu Hospital, Shandong University, Jinan, ChinaRobot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital, Shandong University, Jinan, ChinaAs a major component of the enteroendocrine system, enterochromaffin (EC) cells play a key role in ulcerative colitis (UC). However, the scarcity of EC cells has limited the investigation of their function. In this study, we applied digital spatial profiling to acquire transcriptomic data for EC cells and other epithelial cells from colonoscopic biopsy samples from eight patients with UC and seven healthy controls. Differential expression analysis, gene set enrichment analysis, and weighted gene coexpression network analysis were performed to identify differentially expressed genes and pathways and coexpression networks. Results were validated using an online dataset obtained by single-cell RNA sequencing, along with immunofluorescence staining and quantitative real-time PCR. In healthy participants, 10 genes were significantly enriched in EC cells, functionally concentrated in protein and bioamine synthesis. A coexpression network containing 17 hub genes, including TPH1, CHGA, and GCLC, was identified in EC cells. In patients with UC, EC cells gained increased capacity for protein synthesis, along with novel immunological functions such as antigen processing and presentation, whereas chemical sensation was downregulated. The specific expression of CHGB and RGS2 in EC cells was confirmed by immunofluorescence staining. Our results illuminate the transcriptional signatures of EC cells in the human colon. EC cells’ newly observed functional shift from sensation to secretion and immunity indicates their pivotal role in UC.https://www.frontiersin.org/articles/10.3389/fcell.2022.841090/fullenterochromaffin cellulcerative colitisdigital spatial profilingchromogranin Bsingle-cell RNA-seq |
spellingShingle | Dongping Lyu Dongping Lyu Guanjun Kou Guanjun Kou Shiyang Li Shiyang Li Shiyang Li Lixiang Li Lixiang Li Lixiang Li Bing Li Bing Li Ruchen Zhou Ruchen Zhou Xiaoxiao Yang Xiaoxiao Yang Wenyu Tian Yanqing Li Yanqing Li Yanqing Li Xiuli Zuo Xiuli Zuo Xiuli Zuo Digital Spatial Profiling Reveals Functional Shift of Enterochromaffin Cell in Patients With Ulcerative Colitis Frontiers in Cell and Developmental Biology enterochromaffin cell ulcerative colitis digital spatial profiling chromogranin B single-cell RNA-seq |
title | Digital Spatial Profiling Reveals Functional Shift of Enterochromaffin Cell in Patients With Ulcerative Colitis |
title_full | Digital Spatial Profiling Reveals Functional Shift of Enterochromaffin Cell in Patients With Ulcerative Colitis |
title_fullStr | Digital Spatial Profiling Reveals Functional Shift of Enterochromaffin Cell in Patients With Ulcerative Colitis |
title_full_unstemmed | Digital Spatial Profiling Reveals Functional Shift of Enterochromaffin Cell in Patients With Ulcerative Colitis |
title_short | Digital Spatial Profiling Reveals Functional Shift of Enterochromaffin Cell in Patients With Ulcerative Colitis |
title_sort | digital spatial profiling reveals functional shift of enterochromaffin cell in patients with ulcerative colitis |
topic | enterochromaffin cell ulcerative colitis digital spatial profiling chromogranin B single-cell RNA-seq |
url | https://www.frontiersin.org/articles/10.3389/fcell.2022.841090/full |
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