title: β1-adrenoceptor stimulation enhances the differentiation of mouse induced pluripotent stem cells into neural progenitor cells.
abstract: The cyclic AMP/protein kinase A signaling pathway is thought to be involved in neural differentiation of mesenchymal stem cells. In the present study, we examined the involvement of β-adrenoceptor signaling on the differentiation of mouse induced pluripotent stem (iPS) cells into neural progenitor cells. Mouse iPS cells were cultured on ultra-low-attachment dishes to induce embryoid body (EB) formation. All-trans retinoic acid (ATRA, 1 μM) and/or the β-adrenoceptor agonist l-isoproterenol (0.3 or 1 μM) were added to the EB cultures for 4 days, then EBs were plated on gelatin-coated plates and cultured for 7 or 14 days. Subtype-specific antibody staining revealed that mouse iPS cells express β(1)-adrenoceptors predominantly. Although treatment with l-isoproterenol alone did not affect the expression of Nestin (a specific marker for neural progenitor cells), l-isoproterenol significantly enhanced ATRA-induced Nestin expression. Pretreatment of EBs with either atenolol (a selective β(1)-adrenoceptor antagonist) or H89 (a protein kinase A inhibitor) significantly inhibited the l-isoproterenol-enhancement of ATRA-induced Nestin expression. In addition, the l-isoproterenol treatment significantly enhanced ATRA-induced expression of NeuN (a neuron-specific nuclear protein). These findings suggest that β(1)-adrenoceptor stimulation enhances ATRA-induced neural differentiation of mouse iPS cells.
authors: Department of Pharmacology, National Defense Medical College, Tokorozawa, Saitama, Japan. tishizu@ndmc.ac.jp
authors: Toshiaki
authors: T
authors: Ishizuka
authors: Hazuki
authors: H
authors: Goshima
authors: Ayako
authors: A
authors: Ozawa
authors: Yasuhiro
authors: Y
authors: Watanabe
mesh_terms: D058665:Adrenergic beta-1 Receptor Agonists / Q000494:pharmacology*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D058732:Embryoid Bodies / Q000166:cytology; D005455:Fluorescent Antibody Technique; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007381:Intermediate Filament Proteins / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects*; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism*
chemical_list: D058665:Adrenergic beta-1 Receptor Agonists; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D018342:Receptors, Adrenergic, beta-1; D017868:Cyclic AMP-Dependent Protein Kinases; D007545:Isoproterenol