Examining FKBP5 mRNA expression in human iPSC-derived neural cells. (January 2017)

• Record Type: Journal Article
• Authors: Lieberman, Richard; Kranzler, Henry R.; Levine, Eric S.; Covault, Jonathan
• Is Part Of: Psychiatry research. Volume 247(2017)
• Page Start: 172
• Page End: 181
• Publication Date: 2017-01
• Subjects: FK506 Binding Protein 51 -- Neural differentiation -- Gene expression -- Glucocorticoid receptor -- Fibroblasts -- Induced pluripotent stem cells -- rs1360780; Psychiatry -- Periodicals; Psychiatry -- periodicals; Psychiatrie -- Périodiques; 616.89
• DOI: 10.1016/j.psychres.2016.11.027
• Languages: English
• ISSNs: 0165-1781

Abstract

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 1 μM 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. Highlights: iPSCs differentiate into neurons that express the glucocorticoid receptor and FKBP5. Dexamethasone treatment increased FKBP5 mRNA by 23% in iPSC-derived neural cells. Dexamethasone treatment increased FKBP5 mRNA by 670% in donor-matched fibroblasts. No effect of rs1360780 genotype on FKBP5 mRNA levels were observed.