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

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dc.contributor.authorBlum, Royen_ZA
dc.contributor.authorGupta, Rashmien_ZA
dc.contributor.authorBurger, Patricia Een_ZA
dc.contributor.authorOntiveros, Christopher Sen_ZA
dc.contributor.authorSalm, Sarah Nen_ZA
dc.contributor.authorXiong, Xiaozhongen_ZA
dc.contributor.authorKamb, Alexanderen_ZA
dc.contributor.authorWesche, Holgeren_ZA
dc.contributor.authorMarshall, Lisaen_ZA
dc.contributor.authorCutler, Geneen_ZA
dc.date.accessioned2015-11-18T07:09:09Z
dc.date.available2015-11-18T07:09:09Z
dc.date.issued2010en_ZA
dc.description.abstractBACKGROUND: 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.identifier.apacitationBlum, 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/11427/15134en_ZA
dc.identifier.chicagocitationBlum, 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/11427/15134en_ZA
dc.identifier.citationBlum, 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.0013024en_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
dc.identifier.urihttp://hdl.handle.net/11427/15134
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0013024
dc.identifier.vancouvercitationBlum 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.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentDivision of Immunologyen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis 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.holder© 2010 Blum et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherStem cell nicheen_ZA
dc.subject.otherProstate glanden_ZA
dc.subject.otherProstate canceren_ZA
dc.subject.otherEpidermisen_ZA
dc.subject.otherGene expressionen_ZA
dc.subject.otherGene regulationen_ZA
dc.subject.otherStem cellsen_ZA
dc.titleMolecular signatures of the primitive prostate stem cell niche reveal novel mesenchymal-epithelial signaling pathwaysen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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