Single-Cell Transcriptomics Unravels Growth Factor Erv1-Like Mediated Ferroptosis as a Key Driver of Intestinal...

Area of Science:

• Gastroenterology
• Molecular Biology
• Immunology

Background:

• Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), involves chronic gastrointestinal inflammation with poorly understood mechanisms.
• Epithelial iron homeostasis and cell death regulation are critical but understudied aspects of UC pathogenesis.

Purpose of the Study:

• To investigate the role of GFER in the pathogenesis of ulcerative colitis (UC).
• To explore the relationship between GFER, iron homeostasis, and ferroptosis in intestinal epithelial cells.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) analysis of UC patient intestinal tissues.
• Validation using DSS-induced colitis mouse models and LPS-induced in vitro intestinal epithelial cell inflammation models.
• Investigation of GFER's interaction with PCBP1 and its effect on the PGC-1α/PPARγ signaling pathway.

Main Results:

• GFER expression was significantly downregulated in intestinal epithelial cells of UC patients.
• GFER overexpression inhibited ferroptosis markers and alleviated inflammatory damage in preclinical models.
• GFER interacts with PCBP1 to regulate iron homeostasis and inhibits ferroptosis via the PGC-1α/PPARγ pathway.

Conclusions:

• GFER plays a critical role in regulating ferroptosis in ulcerative colitis.
• This study reveals novel insights into UC pathogenesis and identifies GFER as a potential therapeutic target.