Dataset Information

Lgr4 is a key regulator of prostate development and prostate stem cell differentiation.

ABSTRACT: Mechanisms modulating prostate cell fate determination remain unexplored. The leucine-rich repeat containing G-protein-coupled receptors (Lgr) have been identified as important stem cell markers in various tissues. Here, we investigated the roles of Lgr4/Gpr48 in prostate stem cells (PSCs) and development. Lgr4 was ubiquitously expressed during early prostate development prior to lineage specification, with adult expression restricted to a few basal cells (principally Lin(-)Sca1(+)CD49f(+)). Lgr4(-/-) mice had compromised branching morphogenesis and delayed epithelial differentiation, leading to decreased prostate size and impaired luminal cell function. In vitro prostate sphere culture revealed that Lgr4(-/-) Lin(-)/Sca1(+)/CD49f(+) cells failed to generate p63(low) cells, indicating a differentiation deficiency. Furthermore, Lgr4 ablation arrested PSC differentiation of in vivo kidney capsule prostate grafts, suggesting that Lgr4 modulates PSC properties independent of hormonal and mesenchymal effects. Analysis of neonatal prostates and prostate spheres revealed a decrease in Wnt, Sonic Hedgehog, and Notch1 expression in Lgr4(-/-) cells. Lgr4 loss blocked differentiation of prostate sphere p63(hi) cells to p63(low). Treatment with exogenous Sonic Hedgehog partially restored the differentiation of p63(hi) cells in Lgr4(-/-) spheres. Taken together, our data revealed the roles of Lgr4 in early prostate development and in stem cell differentiation through regulation of the Wnt, Notch, and Sonic Hedgehog signaling pathways.

SUBMITTER: Luo W

PROVIDER: S-EPMC3934101 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Lgr4 is a key regulator of prostate development and prostate stem cell differentiation.

Luo Weijia W Rodriguez Melissa M Valdez Joseph M JM Zhu Xinglei X Tan Kunrong K Li Dali D Siwko Stefan S Xin Li L Liu Mingyao M

Stem cells (Dayton, Ohio) 20131101 11

Mechanisms modulating prostate cell fate determination remain unexplored. The leucine-rich repeat containing G-protein-coupled receptors (Lgr) have been identified as important stem cell markers in various tissues. Here, we investigated the roles of Lgr4/Gpr48 in prostate stem cells (PSCs) and development. Lgr4 was ubiquitously expressed during early prostate development prior to lineage specification, with adult expression restricted to a few basal cells (principally Lin(-)Sca1(+)CD49f(+)). Lgr ...[more]

PMID: 23897697

Similar Datasets

Project description:The capability to derive endothelial cell (ECs) from induced pluripotent stem cells (iPSCs) holds huge therapeutic potential for cardiovascular disease. This study elucidates the precise role of the RNA-binding protein Quaking isoform 5 (QKI-5) during EC differentiation from both mouse and human iPSCs (hiPSCs) and dissects how RNA-binding proteins can improve differentiation efficiency toward cell therapy for important vascular diseases. iPSCs represent an attractive cellular approach for regenerative medicine today as they can be used to generate patient-specific therapeutic cells toward autologous cell therapy. In this study, using the model of iPSCs differentiation toward ECs, the QKI-5 was found to be an important regulator of STAT3 stabilization and vascular endothelial growth factor receptor 2 (VEGFR2) activation during the EC differentiation process. QKI-5 was induced during EC differentiation, resulting in stabilization of STAT3 expression and modulation of VEGFR2 transcriptional activation as well as VEGF secretion through direct binding to the 3' UTR of STAT3. Importantly, mouse iPS-ECs overexpressing QKI-5 significantly improved angiogenesis and neovascularization and blood flow recovery in experimental hind limb ischemia. Notably, hiPSCs overexpressing QKI-5, induced angiogenesis on Matrigel plug assays in vivo only 7 days after subcutaneous injection in SCID mice. These results highlight a clear functional benefit of QKI-5 in neovascularization, blood flow recovery, and angiogenesis. Thus, they provide support to the growing consensus that elucidation of the molecular mechanisms underlying EC differentiation will ultimately advance stem cell regenerative therapy and eventually make the treatment of cardiovascular disease a reality. The RNA binding protein QKI-5 is induced during EC differentiation from iPSCs. RNA binding protein QKI-5 was induced during EC differentiation in parallel with the EC marker CD144. Immunofluorescence staining showing that QKI-5 is localized in the nucleus and stained in parallel with CD144 in differentiated ECs (scale bar = 50 µm). Stem Cells 2017 Stem Cells 2017;35:952-966.

Dataset Information

Lgr4 is a key regulator of prostate development and prostate stem cell differentiation.

Publications

Lgr4 is a key regulator of prostate development and prostate stem cell differentiation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets