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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Main Authors: Dongping Lyu, Guanjun Kou, Shiyang Li, Lixiang Li, Bing Li, Ruchen Zhou, Xiaoxiao Yang, Wenyu Tian, Yanqing Li, Xiuli Zuo
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-04-01
Series:Frontiers in Cell and Developmental Biology
Subjects:
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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