Molecular signatures of the primitive prostate stem cell niche reveal novel mesenchymal-epithelial signaling pathways

 

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dc.contributor.author Blum, Roy en_ZA
dc.contributor.author Gupta, Rashmi en_ZA
dc.contributor.author Burger, Patricia E en_ZA
dc.contributor.author Ontiveros, Christopher S en_ZA
dc.contributor.author Salm, Sarah N en_ZA
dc.contributor.author Xiong, Xiaozhong en_ZA
dc.contributor.author Kamb, Alexander en_ZA
dc.contributor.author Wesche, Holger en_ZA
dc.contributor.author Marshall, Lisa en_ZA
dc.contributor.author Cutler, Gene en_ZA
dc.date.accessioned 2015-11-18T07:09:09Z
dc.date.available 2015-11-18T07:09:09Z
dc.date.issued 2010 en_ZA
dc.identifier.citation Blum, R., Gupta, R., Burger, P. E., Ontiveros, C. S., Salm, S. N., Xiong, X., ... & Wilson, E. L. (2010). Molecular signatures of the primitive prostate stem cell niche reveal novel mesenchymal-epithelial signaling pathways. PloS one, 5(9), e13024. doi:10.1371/journal.pone.0013024 en_ZA
dc.identifier.uri http://hdl.handle.net/11427/15134
dc.identifier.uri http://dx.doi.org/10.1371/journal.pone.0013024
dc.description.abstract 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. en_ZA
dc.language.iso eng en_ZA
dc.publisher Public Library of Science en_ZA
dc.rights This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. en_ZA
dc.rights.uri http://creativecommons.org/licenses/by/4.0 en_ZA
dc.source PLoS One en_ZA
dc.source.uri http://journals.plos.org/plosone en_ZA
dc.subject.other Stem cell niche en_ZA
dc.subject.other Prostate gland en_ZA
dc.subject.other Prostate cancer en_ZA
dc.subject.other Epidermis en_ZA
dc.subject.other Gene expression en_ZA
dc.subject.other Gene regulation en_ZA
dc.subject.other Stem cells en_ZA
dc.title Molecular signatures of the primitive prostate stem cell niche reveal novel mesenchymal-epithelial signaling pathways en_ZA
dc.type Journal Article en_ZA
dc.rights.holder © 2010 Blum et al en_ZA
uct.type.publication Research en_ZA
uct.type.resource Article en_ZA
dc.publisher.institution University of Cape Town
dc.publisher.faculty Faculty of Health Sciences en_ZA
dc.publisher.department Division of Immunology en_ZA
uct.type.filetype Text
uct.type.filetype Image
dc.identifier.apacitation Blum, R., Gupta, R., Burger, P. E., Ontiveros, C. S., Salm, S. N., Xiong, X., ... Cutler, G. (2010). Molecular signatures of the primitive prostate stem cell niche reveal novel mesenchymal-epithelial signaling pathways. <i>PLoS One</i>, http://hdl.handle.net/11427/15134 en_ZA
dc.identifier.chicagocitation Blum, Roy, Rashmi Gupta, Patricia E Burger, Christopher S Ontiveros, Sarah N Salm, Xiaozhong Xiong, Alexander Kamb, Holger Wesche, Lisa Marshall, and Gene Cutler "Molecular signatures of the primitive prostate stem cell niche reveal novel mesenchymal-epithelial signaling pathways." <i>PLoS One</i> (2010) http://hdl.handle.net/11427/15134 en_ZA
dc.identifier.vancouvercitation Blum R, Gupta R, Burger PE, Ontiveros CS, Salm SN, Xiong X, et al. Molecular signatures of the primitive prostate stem cell niche reveal novel mesenchymal-epithelial signaling pathways. PLoS One. 2010; http://hdl.handle.net/11427/15134. en_ZA
dc.identifier.ris TY - Journal Article AU - Blum, Roy AU - Gupta, Rashmi AU - Burger, Patricia E AU - Ontiveros, Christopher S AU - Salm, Sarah N AU - Xiong, Xiaozhong AU - Kamb, Alexander AU - Wesche, Holger AU - Marshall, Lisa AU - Cutler, Gene AB - 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. DA - 2010 DB - OpenUCT DO - 10.1371/journal.pone.0013024 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2010 T1 - Molecular signatures of the primitive prostate stem cell niche reveal novel mesenchymal-epithelial signaling pathways TI - Molecular signatures of the primitive prostate stem cell niche reveal novel mesenchymal-epithelial signaling pathways UR - http://hdl.handle.net/11427/15134 ER - en_ZA


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This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Except where otherwise noted, this item's license is described as This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.