Abstract
Stem cells include a diverse number of toti-, pluri-, and multi-potent cells that play important roles in cellular genesis and differentiation, tissue development, and organogenesis. Genetic regulation involving various transcription factors results in the self-renewal and differentiation properties of stem cells. The nuclear receptor (NR) superfamily is composed of 48 ligand-activated transcription factors involved in diverse physiological functions such as metabolism, development, and reproduction. Increasing evidence shows that certain NRs function in regulating stemness or differentiation of embryonic stem (ES) cells and tissue-specific adult stem cells. Here, we review the role of the NR superfamily in various aspects of stem cell biology, including their regulation of stemness, forward- and trans-differentiation events; reprogramming of terminally differentiated cells; and interspecies differences. These studies provide insights into the therapeutic potential of the NR superfamily in stem cell therapy and in treating stem cell-associated diseases (e.g., cancer stem cell).
Highlights
Stem cells have physiologically unique features including self-renewal and maintenance of unspecialized properties that can be manipulated in the presence of certain stimuli
ES cells are primitive cells derived from various embryonic or fetal stages of development and include three sub-classes: 1) Fertilized embryonic stem cells that are totipotent cells from the fertilized egg to the eight cell stage, 2) blastocyst embryonic stem cells that are pluripotent cells derived from the inner cell mass, and 3) fetal stem cells that are pluripotent cells derived from the fetus itself or multipotent cells from umbilical cord blood
A goal of this review is to provide insight into the potential use of nuclear receptor (NR) superfamily members as both research tools and therapeutic targets for understanding the biology and clinical utility of embryonic, adult, and induced pluripotent stem cells
Summary
Abbreviations: AR, androgen receptor; C/EBP, CCAAT enhancer binding protein; COUP-TF, chicken ovalbumin upstream promoter transcription factor; DAX1, dosage-sensitive sex reversal-adrenal hypoplasia congenita critical region on the X chromosome, gene 1; ER, estrogen receptor; ERR, estrogen-related receptor; ESC, embryonic stem cell; ETO/MTG, eight twenty-one/myeloid translocation gene; GCNF, germ cell nuclear factor; GR, glucocorticoid receptor; GSK3, glycogen synthase kinase 3; HSC, hematopoietic stem cell; iPS, induced pluripotent stem cell; LRH1, liver receptor homolog 1; LXR, liver X receptor; mdDA, meso-diencephalic dopaminergic neuron; MSC, mesenchymal stem cell; NGFI-B, nerve growth factor induced gene B; NOR1, neuron-derived orphan receptor 1; NR, nuclear receptor; NSC, neural stem cell; NURR1, nur-related factor 1; PPAR, peroxisome proliferator-activated receptor; QPCR, quantitative real-time PCR; RAR, retinoic acid receptor; RXR, retinoid X receptor; TCF-4, T-cell nuclear factor 4; TLX, tailless homolog orphan receptor; TR, testicular orphan receptor; VDR, vitamin D receptor
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