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Abstract: The core transcriptional regulatory circuitries are important for controlling stem cell self-renewal and differentiation. Nuclear receptors provide an ideal model to regulate gene expression in both ligand-dependent and ligand-independent manners. Recent studies of regulatory events by nuclear receptors in neural stem cells, embryonic stem cells, and induced pluripotent stem cells (iPSCs) provided unique insights into mechanisms of stem cell regulation and provided invaluable resources for regenerative medicine. Nuclear receptors have been shown to be key players in stem cell self-renewal, pluripotency, and reprogramming. We summarize recent progress of studies on nuclear receptors in stem cell field as well as the potential therapeutic implications of these nuclear receptors and their cognate ligands. These studies not only uncover molecular mechanisms of stem cell regulation, but also provide unique opportunities for drug discovery. [ABSTRACT FROM AUTHOR]

Abstract: Two fundamental properties of stem cells are their ability to self-renew and to differentiate. Self-renewal is an integration of proliferation control with the maintenance of an undifferentiated state. Stem cell self-renewal is regulated by the dynamic interplay between transcription factors, epigenetic control, microRNA (miRNA) regulators, and cell-extrinsic signals from the microenvironment in which stem cells reside. Recent progress in defining specific roles for cell-intrinsic factors and extrinsic factors in regulating stem cell self-renewal starts to unfold the multilayered regulatory networks. This review focuses on cell-intrinsic regulators, including orphan nuclear receptor TLX, polycomb transcriptional repressor Bmi1, high-mobility-group DNA binding protein Sox2, basic helix-loop-helix Hes genes, histone modifying enzymes and chromatin remodeling proteins, and small RNA modulators, as well as cell-extrinsic signaling molecules, such as Wnt, Notch, Sonic hedgehog (Shh), TGFα, EGF, and FGF. Unraveling the mechanisms by which neural stem cells renew themselves will provide insights into both basic neurosciences and clinical applications of stem cell-based cell replacement therapies for neurodegenerative diseases. [Copyright &y& Elsevier]