Nuclear receptor regulation of stemness and stem cell differentiation

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).

Low Molecular Weight Fraction of Commercial Human Serum Albumin Induces Morphologic and Transcriptional Changes of Bone Marrow-Derived Mesenchymal Stem Cells

“…A doubling in signal was deemed significant for this assay, and a representative experiment is presented in Table 2. A number of transcription factors implicated in stem cell differentiation and self-renewal were actively binding oligonucleotide response element probes following LMWF5A treatment, including AP2, COUP-TF, GATA, Gfi-1, Myb, NFAT, PPAR, RXR, SOX2, VDR, and XBP [14][15][16][17][18][19][20][21][22][23][24][25].…”

Endocrine factors in the hypothalamic regulation of food intake in females: a review of the physiological roles and interactions of ghrelin, leptin, thyroid hormones, oestrogen and insulin

“…Thus, oestrogen receptor and thyroid hormone receptor isoforms have modular protein structures with high homology in the central DNA-binding domain where they bind common enhancer elements (ERE) within the promoter sequence modulating gene transcription (280,297,304 -309) . Thyroid hormone receptors and oestrogen receptors are members of the nuclear receptor superfamily, composed of forty-eight ligand-activated Zn-finger transcription factors involved in important physiological functions such as metabolism and energy homeostasis, carbohydrate and lipid metabolism in addition to development, reproduction, etc (304,305,310,311) . Briefly, members of the superfamily of nuclear receptors reside in either the cytoplasm or nucleus of the cell.…”

Embryonic Stem Cells: Introducing Exogenous Regulators into Embryonic Stem Cells

“…It represents a gateway to major future clinical applications of these principles. The levels of transcription factors including nuclear receptors in ES cells are critical in the maintenance of stemness or differentiation of ES cells (Jeong and Mangelsdorf, 2009;Redshaw and Strain, 2010). Certain nuclear receptors are involved in the maintenance of ES cells in cooperation with Oct3/4, Nanog and Klf4 upon exogenous signals.…”

“…Liver receptor homolog 1 (LRH1) and estrogen-related receptor beta (ERR) have functional roles in the maintenance of stemness of ES cells. On the other hand, germ cell nuclear factor (GCNF) and retinoic acid receptors (RARs) promote ES cell differentiation (Jeong and Mangelsdorf, 2009). The Sall gene family that encodes a group of developmental transcription factors controls the embryonic development and is also involved in the determination of ES cell fate.…”