RRC ID 72536
Author Ishizuka T, Goshima H, Ozawa A, Watanabe Y.
Title Stimulation of 5-HT4 receptor enhances differentiation of mouse induced pluripotent stem cells into neural progenitor cells.
Journal Clin Exp Pharmacol Physiol
Abstract Activation of serotonin (5-hydroxytryptamine; 5-HT) receptors plays a role in adult neurogenesis and differentiation of neural progenitor cells (NPC). Herein, we examined the involvement of 5-HT receptors in the differentiation of mouse induced pluripotent stem (iPS) cells into NPC. To induce embryoid body (EB) formation, mouse iPS cells were cultured on ultralow-attachment dishes. All-trans retinoic acid (ATRA; 1 μmol/L) and/or 5-HT (0.03 or 0.1 μmol/L) was added to the EB cultures for 4 days and then EB plated on gelatin-coated plates were cultured for 7 or 14 days. Immunofluorescence staining revealed that mouse iPS cells expressed both 5-HT2A and 5-HT4 receptors and, to a lesser extent, 5-HT1A receptors. Treatment with 5-HT significantly enhanced the ATRA-induced expression of nestin, a specific marker for NPC, and phosphorylation of cAMP response element-binding protein (CREB). Pretreatment of EB cultures with either 1 μmol/L GR113808 (a selective 5-HT4 receptor antagonist) or 1 μmol/L H89 (a protein kinase (PKA) inhibitor) significantly inhibited these effects of 5-HT. These findings suggest that stimulation of 5-HT4 receptors may enhance ATRA-induced neural differentiation of mouse iPS cells through activation of PKA and CREB.
Volume 41(5)
Pages 345-50
Published 2014-5-1
DOI 10.1111/1440-1681.12224
PMID 24606396
MeSH Animals CREB-Binding Protein / metabolism* Cell Culture Techniques Cell Differentiation / drug effects* Cell Differentiation / physiology Cell Line Cyclic AMP-Dependent Protein Kinases / metabolism* Indoles / pharmacology Induced Pluripotent Stem Cells / cytology Induced Pluripotent Stem Cells / drug effects* Induced Pluripotent Stem Cells / metabolism Mice Microscopy, Fluorescence Neural Stem Cells / cytology Neural Stem Cells / drug effects* Neural Stem Cells / metabolism Phosphorylation Protein Kinase Inhibitors / pharmacology Receptors, Serotonin, 5-HT4 / metabolism* Serotonin / pharmacology Serotonin 5-HT4 Receptor Agonists / pharmacology Serotonin 5-HT4 Receptor Antagonists / pharmacology Sulfonamides / pharmacology
Human and Animal Cells iPS-MEF-Ng-20D-17(APS0001)