Leucine-rich repeat containing G protein-coupled receptor 5 (Lgr5), a marker of intestinal stem cells (ISCs), is considered to play key roles in tissue homoeostasis and regeneration after acute radiation injury. However, the activation of Lgr5 by integrated signaling pathways upon radiation remains poorly understood. Here, we show that irradiation of mice with whole-body depletion or conditional ablation of REGγ in Lgr5 stem cell impairs proliferation of intestinal crypts, delaying regeneration of intestine epithelial cells. Mechanistically, REGγ enhances transcriptional activation of Lgr5 via the potentiation of both Wnt and Hippo signal pathways. TEAD4 alone or cooperates with TCF4, a transcription factor mediating Wnt signaling, to enhance the expression of Lgr5. Silencing TEAD4 drastically attenuated β-catenin/TCF4 dependent expression of Lgr5. Together, our study reveals how REGγ controls Lgr5 expression and expansion of Lgr5 stem cells in the regeneration of intestinal epithelial cells. Thus, REGγ proteasome appears to be a potential therapeutic target for radiation-induced gastrointestinal disorders.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s11427-021-2018-7 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
LGR5: An emerging therapeutic target for cancer metastasis and chemotherapy resistance.
Cancer Metastasis Rev
January 2025
Discipline of Obstetrics and Gynaecology, Adelaide Medical School, Robinson Research Institute, The University of Adelaide, Adelaide, 5005, Australia.
Cancer stem cells play an important role in tumor progression and chemotherapy resistance. Leucine-rich G repeat-containing protein-coupled receptor 5 (LGR5) has been identified as a cancer stem cell marker in several cancer types. LGR5 is involved in cancer development and progression via several pathways including WNT/β-catenin signaling pathway.
View Article and Find Full Text PDFFate mapping in mouse demonstrates early secretory differentiation directly from Lgr5+ intestinal stem cells.
Dev Cell
January 2025
Novo Nordisk Foundation Center for Stem Cell Medicine, reNEW, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen N, Denmark. Electronic address:
The intestinal epithelium has a remarkably high turnover in homeostasis. It remains unresolved how this is orchestrated at the cellular level and how the behavior of stem and progenitor cells ensures tissue maintenance. To address this, we combined quantitative fate mapping in three complementary mouse models with mathematical modeling and single-cell RNA sequencing.
View Article and Find Full Text PDFE-cigarettes increase the risk of adenoma formation in murine colorectal cancer model.
Arch Toxicol
January 2025
Department of Medicine, University of California, San Diego, CA, 92093, USA.
E-cigarettes (E.cigs) cause inflammation and damage to human organs, including the lungs and heart. In the gut, E.
View Article and Find Full Text PDFMouse Intestinal Organoid Culture Protocol.
Methods Mol Biol
January 2025
Faculty of Engineering, Genetics and Bioengineering Department, Yeditepe University, İstanbul, Turkey.
The discovery of leucine-rich-containing G-protein-coupled receptor 5 (Lgr5) as an intestinal adult stem cell marker had blazed a trail in stem cell biology and laid the foundations of modern organoid technology. Up to date, several well-established intestinal organoid protocols have been reported in the literature from different sources, including adult and induced pluripotent stem cells. Here, we demonstrate a BALB/c mouse-derived intestinal organoid culture protocol, passaging, and cryopreservation procedures.
View Article and Find Full Text PDFFunctional and Biological Characterization of the LGR5Δ5 Splice Variant in HEK293T Cells.
Int J Mol Sci
December 2024
Department of Oral and Maxillofacial Plastic Surgery, Faculty of Medicine, Martin Luther University Halle-Wittenberg, 06120 Halle, Germany.
The regulator of the canonical Wnt pathway, leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), is expressed in the stem cell compartment of several tissues and overexpressed in different human carcinomas. The isoform of the stem cell marker LGR5, named LGR5Δ5 and first described by our group, is associated with prognosis and metastasis in oral squamous cell carcinoma (OSCC) and soft tissue sarcoma (STS). In a proof-of-principle analysis, the function of LGR5Δ5 was investigated in HEK293T cells, a model cell line of the Wnt pathway, compared to full-length LGR5 (FL) expression.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!