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      The Androgen Receptor Bridges Stem Cell-Associated Signaling Nodes in Prostate Stem Cells

      review-article
      Author(s): 1 , 1 , 2 , *
      Publication date (Electronic):
      Journal: Stem Cells International
      Publisher: Hindawi Publishing Corporation

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          Abstract

          The therapeutic potential of stem cells relies on dissecting the complex signaling networks that are thought to regulate their pluripotency and self-renewal. Until recently, attention has focused almost exclusively on a small set of “core” transcription factors for maintaining the stem cell state. It is now clear that stem cell regulatory networks are far more complex. In this review, we examine the role of the androgen receptor (AR) in coordinating interactions between signaling nodes that govern the balance of cell fate decisions in prostate stem cells.

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          Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells.

          Ian Chambers, Douglas Colby, Morag Robertson … (2003)
          Embryonic stem (ES) cells undergo extended proliferation while remaining poised for multilineage differentiation. A unique network of transcription factors may characterize self-renewal and simultaneously suppress differentiation. We applied expression cloning in mouse ES cells to isolate a self-renewal determinant. Nanog is a divergent homeodomain protein that directs propagation of undifferentiated ES cells. Nanog mRNA is present in pluripotent mouse and human cell lines, and absent from differentiated cells. In preimplantation embryos, Nanog is restricted to founder cells from which ES cells can be derived. Endogenous Nanog acts in parallel with cytokine stimulation of Stat3 to drive ES cell self-renewal. Elevated Nanog expression from transgene constructs is sufficient for clonal expansion of ES cells, bypassing Stat3 and maintaining Oct4 levels. Cytokine dependence, multilineage differentiation, and embryo colonization capacity are fully restored upon transgene excision. These findings establish a central role for Nanog in the transcription factor hierarchy that defines ES cell identity.
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            Stem cells and niches: mechanisms that promote stem cell maintenance throughout life.

            Sean Morrison, Allan Spradling (2008)
            Niches are local tissue microenvironments that maintain and regulate stem cells. Long-predicted from mammalian studies, these structures have recently been characterized within several invertebrate tissues using methods that reliably identify individual stem cells and their functional requirements. Although similar single-cell resolution has usually not been achieved in mammalian tissues, principles likely to govern the behavior of niches in diverse organisms are emerging. Considerable progress has been made in elucidating how the microenvironment promotes stem cell maintenance. Mechanisms of stem cell maintenance are key to the regulation of homeostasis and likely contribute to aging and tumorigenesis when altered during adulthood.
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              Connecting microRNA genes to the core transcriptional regulatory circuitry of embryonic stem cells.

              Alexander Marson, Stuart S. Levine, Megan Cole … (2008)
              MicroRNAs (miRNAs) are crucial for normal embryonic stem (ES) cell self-renewal and cellular differentiation, but how miRNA gene expression is controlled by the key transcriptional regulators of ES cells has not been established. We describe here the transcriptional regulatory circuitry of ES cells that incorporates protein-coding and miRNA genes based on high-resolution ChIP-seq data, systematic identification of miRNA promoters, and quantitative sequencing of short transcripts in multiple cell types. We find that the key ES cell transcription factors are associated with promoters for miRNAs that are preferentially expressed in ES cells and with promoters for a set of silent miRNA genes. This silent set of miRNA genes is co-occupied by Polycomb group proteins in ES cells and shows tissue-specific expression in differentiated cells. These data reveal how key ES cell transcription factors promote the ES cell miRNA expression program and integrate miRNAs into the regulatory circuitry controlling ES cell identity.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Stem Cells Int
                Journal ID (iso-abbrev): Stem Cells Int
                Journal ID (publisher-id): SCI
                Title: Stem Cells International
                Publisher: Hindawi Publishing Corporation
                ISSN (Print): 1687-966X
                ISSN (Electronic): 1687-9678
                Publication date (Print): 2016
                Publication date (Electronic): 10 January 2016
                Volume: 2016
                Electronic Location Identifier: 4829602
                Affiliations
                1Vancouver Prostate Centre, Vancouver, BC, Canada V6H 3Z6
                2Department of Urologic Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada V6H 3Z6
                Author notes

                Academic Editor: Hu Li

                Article
                DOI: 10.1155/2016/4829602
                PMC ID: 4737002
                PubMed ID: 26880966
                SO-VID: 8ea5bd3a-14ad-4bf4-af68-e353f9c50a65
                Copyright © Copyright © 2016 A. H. Davies and A. Zoubeidi.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 30 September 2015
                Date revision received : 4 December 2015
                Date accepted : 13 December 2015
                Categories
                Subject: Review Article

                ScienceOpen disciplines: Molecular medicine
                Data availability:
                ScienceOpen disciplines: Molecular medicine

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