Neuronal cells derived from human induced pluripotent stem cells as a functional tool of melanocortin system.
BACKGROUND
The preparation of human neurons derived from human induced pluripotent stem (iPS) cells can serve as a potential tool for evaluating the physiological and pathophysiological properties of human neurons and for drug development.


METHODS
In the present study, the functional activity in neuronal cells differentiated from human iPS cells was observed.


RESULTS
The differentiated cells expressed mRNAs for classical neuronal markers (microtubule-associated protein 2, β-tubulin III, calbindin 1, synaptophysin and postsynaptic density protein 95) and for subunits of various excitatory and inhibitory transmitters (NR1, NR2A, NR2B, GABAA α1). Moreover, the differentiated cells expressed neuropeptides and receptors which are predominantly present in the hypothalamus. The expression of mRNA for preopiomelanocortin, agouti-related protein (AgRP), melanocortin-3 receptor (MC3R) and melanocortin-4 receptor (MC4R) increased in culture with a peak on Day 30 which subsequently decreased at Day 45. Immunoreactivities for MC3R and MC4R were also observed in cells differentiated from human iPS cells. Application of a potent agonist for MC3R and MC4R, [Nle4, D-Phe7]-α-melanocyte-stimulating hormone, significantly increased intracellular cAMP levels, but this was suppressed by AgRP (83-132) and SHU9119.


CONCLUSIONS
These findings offer the possibility for drug developments using neurons differentiated from normal or disease-associated human iPS cells.
['Yamada-Goto|Nobuko|N|', 'Ochi|Yukari|Y|', 'Katsuura|Goro|G|', 'Yamashita|Yui|Y|', 'Ebihara|Ken|K|', 'Noguchi|Michio|M|', 'Fujikura|Junji|J|', 'Taura|Daisuke|D|', 'Sone|Masakatsu|M|', 'Hosoda|Kiminori|K|', 'Gottschall|Paul E|PE|', 'Nakao|Kazuwa|K|']
D000328:Adult D002454:Cell Differentiation D002478:Cells, Cultured D005260:Female D006801:Humans D057026:Induced Pluripotent Stem Cells D053486:Melanocortins D009474:Neurons D021122:Protein Subunits D012333:RNA, Messenger D018079:Receptors, GABA D016194:Receptors, N-Methyl-D-Aspartate
Neuronal cells Melanocortin system Human iPS cells Neuropeptides cAMP Food intake