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Updated: May 9, 2026
10:38
Evaluating the Differentiation Capacity of Mouse Prostate Epithelial Cells Using Organoid Culture
Published on: November 22, 2019
Lgr4 is a key regulator of prostate development and prostate stem cell differentiation
Weijia Luo1, Melissa Rodriguez, Joseph M Valdez
1Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, TexasA&M University Health Science Center, Houston, Texas, USA.
Stem Cells (Dayton, Ohio)
|July 31, 2013
Summary
Leucine-rich repeat-containing G-protein-coupled receptors 4 (Lgr4) are crucial for prostate stem cell differentiation. Lgr4 deficiency impairs prostate development and epithelial cell maturation by disrupting Wnt, Notch, and Sonic Hedgehog signaling pathways.
Area of Science:
- Urology
- Developmental Biology
- Stem Cell Biology
Background:
- Prostate cell fate determination mechanisms are not well understood.
- Leucine-rich repeat-containing G-protein-coupled receptors (Lgr) are recognized stem cell markers in various tissues.
Purpose of the Study:
- To investigate the role of Lgr4/Gpr48 in prostate stem cells (PSCs) and prostate development.
- To elucidate the signaling pathways regulated by Lgr4 in prostate stem cell differentiation.
Main Methods:
- Utilized Lgr4(-/-) mice and in vitro prostate sphere cultures.
- Analyzed gene expression of Wnt, Sonic Hedgehog, and Notch1.
- Performed in vivo kidney capsule prostate grafting experiments.
Main Results:
- Lgr4(-/-) mice exhibited impaired prostate branching morphogenesis, delayed epithelial differentiation, reduced prostate size, and compromised luminal cell function.
- Lgr4(-/-) prostate stem cells failed to differentiate into p63(low) cells in vitro and in vivo.
- Lgr4 deficiency led to decreased Wnt, Sonic Hedgehog, and Notch1 expression, and exogenous Sonic Hedgehog partially rescued differentiation.
Conclusions:
- Lgr4 plays a critical role in early prostate development and stem cell differentiation.
- Lgr4 regulates prostate stem cell properties independently of hormonal and mesenchymal influences.
- Lgr4 modulates prostate stem cell differentiation through the Wnt, Notch, and Sonic Hedgehog signaling pathways.
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