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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Molecular signatures of the primitive prostate stem cell niche reveal novel mesenchymal-epithelial signaling pathways
PLoS ONE, Volume 5, No. 9, Article e13024, Year 2010
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Description
Background: Signals between stem cells and stroma are important in establishing the stem cell niche. However, very little is known about the regulation of any mammalian stem cell niche as pure isolates of stem cells and their adjacent mesenchyme are not readily available. The prostate offers a unique model to study signals between stem cells and their adjacent stroma as in the embryonic prostate stem cell niche, the urogenital sinus mesenchyme is easily separated from the epithelial stem cells. Here we investigate the distinctive molecular signals of these two stem cell compartments in a mammalian system. Methodology/Principal Findings: We isolated fetal murine urogenital sinus epithelium and urogenital sinus mesenchyme and determined their differentially expressed genes. To distinguish transcripts that are shared by other developing epithelial/mesenchymal compartments from those that pertain to the prostate stem cell niche, we also determined the global gene expression of epidermis and dermis of the same embryos. Our analysis indicates that several of the key transcriptional components that are predicted to be active in the embryonic prostate stem cell niche regulate processes such as self-renewal (e.g., E2f and Ap2), lipid metabolism (e.g., Srebp1) and cell migration (e.g., Areb6 and Rreb1). Several of the enriched promoter binding motifs are shared between the prostate epithelial/mesenchymal compartments and their epidermis/dermis counterparts, indicating their likely relevance in epithelial/mesenchymal signaling in primitive cellular compartments. Based on differential gene expression we also defined ligand-receptor interactions that may be part of the molecular interplay of the embryonic prostate stem cell niche. Conclusions/Significance: We provide a comprehensive description of the transcriptional program of the major regulators that are likely to control the cellular interactions in the embryonic prostatic stem cell niche, many of which may be common to mammalian niches in general. This study provides a comprehensive source for further studies of mesenchymal/epithelial interactions in the prostate stem cell niche. The elucidation of pathways in the normal primitive niche may provide greater insight into mechanisms subverted during abnormal proliferative and oncogenic processes. Understanding these events may result in the development of specific targeted therapies for prostatic diseases such as benign prostatic hypertrophy and carcinomas. © 2010 Blum et al.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC2948007/bin/pone.0013024.s001.xls
https://efashare.b-cdn.net/share/pmc/articles/PMC2948007/bin/pone.0013024.s002.xls
https://efashare.b-cdn.net/share/pmc/articles/PMC2948007/bin/pone.0013024.s003.xls
https://efashare.b-cdn.net/share/pmc/articles/PMC2948007/bin/pone.0013024.s004.xls
https://efashare.b-cdn.net/share/pmc/articles/PMC2948007/bin/pone.0013024.s005.xls
Authors & Co-Authors
Blum, Roy
United States, New York
Nyu Grossman School of Medicine
Gupta, Rashmi
United States, New York
Nyu Grossman School of Medicine
Burger, Patricia E.
South Africa, Cape Town
University of Cape Town
Ontiveros, Christopher S.
United States, New York
Nyu Grossman School of Medicine
Salm, Sarah N.
United States, New York
Nyu Grossman School of Medicine
United States, New York
The City University of new York
Xiong, Xiaozhong
United States, New York
Nyu Grossman School of Medicine
Kamb, Alexander
United States, Thousand Oaks
Amgen Incorporated
Wesche, Holger
United States, Thousand Oaks
Amgen Incorporated
Marshall, Lisa
United States, Thousand Oaks
Amgen Incorporated
Cutler, Gene
United States, Thousand Oaks
Amgen Incorporated
Wang, Xiangyun
United States, New York
Pfizer Inc.
Zavadil, Jiří
United States, New York
Nyu Grossman School of Medicine
United States, New York
Nyu Langone Health
Moscatelli, David
United States, New York
Nyu Grossman School of Medicine
Wilson, Elaine Lynette
United States, New York
Nyu Grossman School of Medicine
South Africa, Cape Town
University of Cape Town
Statistics
Citations: 26
Authors: 14
Affiliations: 6
Identifiers
Doi:
10.1371/journal.pone.0013024
e-ISSN:
19326203
Research Areas
Cancer
Genetics And Genomics