Single-cell transcriptomic profiling uncovers cellular complexity and microenvironment in gastric tumorigenesis associated with Helicobacter pylori - Research focus and findings

Sep 21, 2026

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Helicobacter pylori infection is a major risk factor for gastric cancer, yet the cellular heterogeneity and molecular mechanisms in H. pylori-driven tumorigenesis remain incompletely characterized. The study builds a single-cell atlas across gastritis, gastric intestinal metaplasia, and gastric cancer with or without H. pylori, using single-cell RNA sequencing and validating selected signals in an independent tissue cohort. Results define cancer-associated cell lineages, characterize epithelial enterocytes and DEGs, and reveal enriched cell-cell communication with active TNF signaling.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages21

Reading Time53 min

AccessFree to download

Introduction

Objective

Methods

Single-cell RNA sequencing and validation

Bioinformatics analyses

Results

Cellular heterogeneity across progression

Enterocyte features and HNF4G prediction

Differential expression and cell-cell communication

Conclusions

Journal of Advanced Research 74 (2025) 471–491 Contents lists available at ScienceDirect Journal of Advanced Research journal [homepage: www. elsevier. com/locate/jare](homepage: www. elsevier. com/locate/jare) Single-cell transcriptomic proﬁling uncovers cellular complexity and microenvironment in gastric tumorigenesis associated with Helicobacter pylori Nianshuang Li a, 1, Sihai Chen a,b, 1, Xinbo Xu a, 1, Huan Wang a,b, Pan Zheng a, Xiao Fei a, Huajing Ke a, Yuting Lei a, Yanan Zhou a, Xiaoyu Yang a, Yaobin Ouyang a, Chuan Xie a, Cong He a, Yi Hu a, Yi Cao c, Zhengrong Li c, Yong Xie a, Zhongming Ged, Xu Shu a, Nonghua Lu a, ⇑, Jianping Liu a, ⇑, Yin Zhu a, ⇑ a Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Afﬁliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China b Postdoctoral Innovation Practice Base, The First Afﬁliated Hospital of Nanchang University, Nanchang, Jiangxi, China c Department of General Surgery, The First Afﬁliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China d Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA h i g h l i g h t s ScRNA-seq data revealed cellular heterogeneity in gastric tumorigenesis. Enterocytes, was overwhelmingly abundant in gastric intestinal metaplasia lesion. HNF4G was predicted as the speciﬁc transcription factor. ScRNA-seq unveiled the transcriptional features of distinct cell subtypes in GC. The differentia expressed genes (DEGs) in epithelial, ﬁbroblasts and myeolid cells associated with H. pylori infection have been identiﬁed. H. pylori-positive specimens exhibited enriched cell-cell communication, with signiﬁcant active TNF signaling network. g r a p h i c a l a b s t r a c t Graphical summary of cellular heterogeneity and microenvironment along the consecutive gastric carcinogenesis associated with H. pylori. (A) Cellular heterogeneity along the histological cascade of gastric carcinogenesis with or without H. pylori infection. (B) The DEGs between H. pylori ~~ ~~ positive and negative cell types. GS, gastritis; IM, intestinal metaplasia; GC, gastric cancer. a r t i c l e i n f o Article history: Received 29 June 2024 Revised 11 October 2024 Accepted 11 October 2024 Available online 15 October 2024 Keywords: scRNA-seq Cellular heterogeneity a b s t r a c t Introduction: Helicobacter pylori (H. pylori) infection is the main risk for gastric cancer (GC). However, the cellular heterogeneity and underlying molecular mechanisms in H. pylori-driven gastric tumorigenesis are poorly understood. Objective: Here, we generated a single-cell atlas of gastric tumorigenesis comprising 18 specimens of gastritis, gastric intestinal metaplasia (IM) and GC with or without H. pylori infection. Methods: Single-cell RNA sequencing (scRNA-seq) was performed. Immunoﬂuorescence, immunohistochemistry and qRT-PCR analysis were applied in a second human gastric tissues cohort for validation. Bioinformatics analyses of public TCGA and GEO datasets were applied. ⇑ Corresponding authors at: Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Afﬁliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China. E-mail addresses: [lunonghua@ncu.edu.cn](lunonghua@ncu.edu.cn) (N. Lu), [ndyfy10307@ncu.edu.cn](ndyfy10307@ncu.edu.cn) (J. Liu), [ndyfy01977@ncu.edu.cn](ndyfy01977@ncu.edu.cn) (Y. Zhu). 1 These authors contributed equally to the study. [https://doi.org/10.1016/j.jare.2024.10.012](https://doi.org/10.1016/j.jare.2024.10.012) 2090-1232/􀀁 2024 The Authors. Published by Elsevier B.V. on behalf of Cairo University. This is an open access artic

FAQs

What is the main objective of the study on H. pylori and gastric tumorigenesis?

To construct a single-cell atlas of gastric tumorigenesis across gastritis, intestinal metaplasia, and gastric cancer, and to uncover cellular heterogeneity and molecular mechanisms associated with H. pylori.

How was cellular heterogeneity investigated?

Single-cell RNA sequencing (scRNA-seq) was used to profile samples across disease stages, with immunofluorescence, immunohistochemistry, and qRT-PCR applied to validate findings in a separate tissue cohort.

What key microenvironmental communication signals were reported in H. pylori-positive specimens?

H. pylori-positive specimens showed enriched cell-cell communication with significantly active TNF signaling, along with other networks including SPP1 and THY1.

Sep 21, 2026

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