AUTHOR=Chen Ruofei , Zhang Xiao , Shang Yifang , Zhang Huaixuan , Li Xiaolei , Dai Hanren , Shuai Zongwen 

TITLE=Investigation of the role of GEM in systemic lupus erythematosus through multi-omics joint analysis

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1569605

DOI=10.3389/fimmu.2025.1569605

ISSN=1664-3224

ABSTRACT=BackgroundSystemic lupus erythematosus (SLE) is a persistent autoimmune disorder marked by dysregulation of the immune system, resulting in extensive tissue inflammation and subsequent damage. Fibroblasts are essential contributors to the pathogenesis of SLE, particularly in driving the progression of tissue fibrosis and inflammation. Recent research has proposed that the GEM gene may regulate fibroblast activity in SLE. However, the precise molecular mechanisms through which GEM modulates fibroblast functions in the context of SLE are yet to be fully elucidated. Gaining insight into these mechanisms is crucial for uncovering potential therapeutic targets aimed at addressing fibrosis and inflammation associated with SLE.MethodsSingle-cell RNA sequencing was integrated with cell-based assays, such as quantitative reverse transcription PCR (qRT-PCR) and functional cellular experiments, to investigate the underlying mechanisms. The regulatory mechanisms of GEM in fibroblasts were analyzed through functional cell assays.ResultsDifferential gene expression in fibroblast subpopulations was identified through single-cell RNA sequencing, with GEM emerging as a key gene implicated in these alterations. Trajectory analysis indicated that GEM expression correlated with fibroblast proliferation and migration. Subsequent experiments confirmed that GEM regulates fibroblast viability and influences SLE disease progression through modulation of cell proliferation, migration, and apoptosis.ConclusionsGEM is highly differentially expressed in fibroblast subpopulations within SLE, and its altered expression impacts fibroblast proliferation and migration. GEM may regulate fibroblast activity and apoptosis, potentially contributing to the progression of SLE.