Expression profiles of the nuclear receptors and their transcriptional coregulators during differentiation of neural stem cells

A. Androutsellis-Theotokis, G. P. Chrousos, R. D. McKay, A. H. Decherney, Tomoshige Kino

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Neural stem cells (NSCs) are pluripotent precursors with the ability to proliferate and differentiate into 3 neural cell lineages, neurons, astrocytes and oligodendrocytes. Elucidation of the mechanisms underlying these biologic processes is essential for understanding both physiologic and pathologic neural development and regeneration after injury. Nuclear hormone receptors (NRs) and their transcriptional coregulators also play crucial roles in neural development, functions and fate. To identify key NRs and their transcriptional regulators in NSC differentiation, we examined mRNA expression of 49 NRs and many of their coregulators during differentiation (0-5 days) of mouse embryonic NSCs induced by withdrawal of fibroblast growth factor-2 (FGF2). 37 out of 49 NRs were expressed in NSCs before induction of differentiation, while receptors known to play major roles in neural development, such as THRα, RXRs, RORs, TRs, and COUP-TFs, were highly expressed. CAR, which plays important roles in xenobiotic metabolism, was also highly expressed. FGF2 withdrawal induced mRNA expression of RORγ, RXRγ, and MR by over 20-fold. Most of the transcriptional coregulators examined were expressed basally and throughout differentiation without major changes, while FGF2 withdrawal strongly induced mRNA expression of several histone deacetylases (HDACs), including HDAC11. Dexamethasone and aldosterone, respectively a synthetic glucocorticoid and natural mineralocorticoid, increased NSC numbers and induced differentiation into neurons and astrocytes. These results indicate that the NRs and their coregulators are present and/or change their expression during NSC differentiation, suggesting that they may influence development of the central nervous system in the absence or presence of their ligands.

Original languageEnglish
Pages (from-to)159-168
Number of pages10
JournalHormone and Metabolic Research
Volume45
Issue number2
DOIs
Publication statusPublished - 2013
Externally publishedYes

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Neural Stem Cells
Cytoplasmic and Nuclear Receptors
Stem cells
Fibroblast Growth Factor 2
Astrocytes
Messenger RNA
Neurons
Cell Differentiation
Mineralocorticoids
Histone Deacetylases
Oligodendroglia
Neurology
Cell Lineage
Xenobiotics
Aldosterone
Metabolism
Dexamethasone
Glucocorticoids
Regeneration
Central Nervous System

Keywords

  • central nervous system
  • glucocorticoid
  • histone deacetylase
  • mineralocorticoid
  • neuron

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism

Cite this

Expression profiles of the nuclear receptors and their transcriptional coregulators during differentiation of neural stem cells. / Androutsellis-Theotokis, A.; Chrousos, G. P.; McKay, R. D.; Decherney, A. H.; Kino, Tomoshige.

In: Hormone and Metabolic Research, Vol. 45, No. 2, 2013, p. 159-168.

Research output: Contribution to journalArticle

Androutsellis-Theotokis, A. ; Chrousos, G. P. ; McKay, R. D. ; Decherney, A. H. ; Kino, Tomoshige. / Expression profiles of the nuclear receptors and their transcriptional coregulators during differentiation of neural stem cells. In: Hormone and Metabolic Research. 2013 ; Vol. 45, No. 2. pp. 159-168.
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