title: Examining FKBP5 mRNA expression in human iPSC-derived neural cells.
abstract: In peripheral blood leukocytes, FKBP5 mRNA expression is upregulated following glucocorticoid receptor activation. The single nucleotide polymorphism rs1360780 in FKBP5 is associated with psychiatric illness and has functional molecular effects. However, examination of FKBP5 regulation has largely been limited to peripheral cells, which may not reflect regulation in neural cells. We used 27 human induced pluripotent stem cell lines (iPSCs) derived from 20 subjects to examine FKBP5 mRNA expression following GR activation. Following differentiation into forebrain-lineage neural cultures, cells were exposed to 1μM dexamethasone and mRNA expression of FKBP5 and NR3C1 analyzed. Results from the iPSC-derived neural cells were compared with those from 15 donor matched fibroblast lines. Following dexamethasone treatment, there was a 670% increase in FKBP5 expression in fibroblasts, mimicking findings in peripheral blood-derived cells, but only a 23% increase in iPSC-derived neural cultures. FKBP5 rs1360780 genotype did not affect the induction of FKBP5 mRNA in either fibroblasts or neural cells. These results suggest that iPSC-derived forebrain-lineage neurons may not be an optimal neural cell type in which to examine relationships between GR activation, FKBP5 expression, and genetic variation in human subjects. Further, FKBP5 induction following GR activation may differ between cell types derived from the same individual.
authors.affiliation: Alcohol Research Center, Department of Psychiatry, University of Connecticut School of Medicine, Farmington 06030-1410, CT, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Lieberman
authors.affiliation: Center for Studies of Addiction, Department of Psychiatry, Perelman School of Medicine of the University of Pennsylvania, Philadelphia 19104, PA, USA; VISN4 MIRECC, Crescenz Philadelphia VAMC, Philadelphia 19104, PA, USA.
authors.forename: Henry R
authors.initials: HR
authors.lastname: Kranzler
authors.affiliation: Department of Neuroscience, University of Connecticut School of Medicine, Farmington 06030, CT, USA.
authors.forename: Eric S
authors.initials: ES
authors.lastname: Levine
authors.affiliation: Alcohol Research Center, Department of Psychiatry, University of Connecticut School of Medicine, Farmington 06030-1410, CT, USA. Electronic address: jocovault@uchc.edu.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Covault
mesh_terms: D003907:Dexamethasone / Q000494:pharmacology*; D005838:Genotype; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000502:physiology; D058953:Neural Stem Cells / Q000187:drug effects*; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000187:drug effects; D022021:Tacrolimus Binding Proteins / Q000235:genetics*; D000099159:Tacrolimus Binding Protein 5
chemical_list: D003907:Dexamethasone; D005938:Glucocorticoids; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5
keywords: FK506 Binding Protein 51; Fibroblasts; Gene expression; Glucocorticoid receptor; Induced pluripotent stem cells; Neural differentiation; rs1360780