Identification of Novel Population-Specific Cell Subsets in Chinese Ulcerative Colitis Patients Using Single-Cell RNA Sequencing

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved..

BACKGROUND & AIMS: Genome-wide association studies (GWAS) and transcriptome analyses have been performed to better understand the pathogenesis of ulcerative colitis (UC). However, current studies mainly focus on European ancestry, highlighting a great need to identify the key genes, pathways and cell types in colonic mucosal cells of adult UC patients from other ancestries. Here we aimed to identify key genes and cell types in colonic mucosal of UC.

METHODS: We performed Single-cell RNA sequencing (scRNA-seq) analysis of 12 colon biopsies of UC patients and healthy controls from Chinese Han ancestry.

RESULTS: Two novel plasma subsets were identified. Five epithelial/stromal and three immune cell subsets show significant difference in abundance between inflamed and non-inflamed samples. In general, UC risk genes show consistent expression alteration in both Immune cells of inflamed and non-inflamed tissues. As one of the exceptions, IgA defection, marking the signal of immune dysfunction, is specific to the inflamed area. Moreover, Th17 derived activation was observed in both epithelial cell lineage and immune cell lineage of UC patients as compared to controls , suggesting a systemic change of immune activities driven by Th17. The UC risk genes show enrichment in progenitors, glial cells and immune cells, and drug-target genes are differentially expressed in antigen presenting cells.

CONCLUSIONS: Our work identifies novel population-specific plasma cell molecular signatures of UC. The transcriptional signature of UC is shared in immune cells from both inflamed and non-inflamed tissues, whereas the transcriptional response to disease is a local effect only in inflamed epithelial/stromal cells.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:12

Enthalten in:

Cellular and molecular gastroenterology and hepatology - 12(2021), 1 vom: 01., Seite 99-117

Sprache:

Englisch

Beteiligte Personen:

Li, Guang [VerfasserIn]
Zhang, Bowen [VerfasserIn]
Hao, Jianyu [VerfasserIn]
Chu, Xiaojing [VerfasserIn]
Wiestler, Miriam [VerfasserIn]
Cornberg, Markus [VerfasserIn]
Xu, Cheng-Jian [VerfasserIn]
Liu, Xinjuan [VerfasserIn]
Li, Yang [VerfasserIn]

Links:

Volltext

Themen:

Genome-Wide Association Studies
Journal Article
Research Support, Non-U.S. Gov't
Single-Cell RNA Sequencing
Ulcerative Colitis

Anmerkungen:

Date Completed 24.01.2022

Date Revised 24.01.2022

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.jcmgh.2021.01.020

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM321060008