Neuronal cells derived from human induced pluripotent stem cells as a functional tool of melanocortin system

Nobuko Goto, Yukari Ochi, Goro Katsuura, Yui Yamashita, Ken Ebihara, Michio Noguchi, Junji Fujikura, Daisuke Taura, Masakatsu Sone, Kiminori Hosoda, Paul E. Gottschall, Kazuwa Nakao

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)10-20
Number of pages11
JournalNeuropeptides
Volume65
DOIs
Publication statusPublished - 2017 Oct 1
Externally publishedYes

Fingerprint

Melanocortins
Induced Pluripotent Stem Cells
Receptor, Melanocortin, Type 3
Receptor, Melanocortin, Type 4
Neurons
Agouti-Related Protein
Calbindin 1
Neuropeptide Receptors
Melanocyte-Stimulating Hormones
Messenger RNA
Synaptophysin
Microtubule-Associated Proteins
Protein Subunits
Tubulin
Pharmaceutical Preparations
Hypothalamus

Keywords

  • cAMP
  • Food intake
  • Human iPS cells
  • Melanocortin system
  • Neuronal cells
  • Neuropeptides

ASJC Scopus subject areas

  • Endocrinology
  • Neurology
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience

Cite this

Neuronal cells derived from human induced pluripotent stem cells as a functional tool of melanocortin system. / Goto, Nobuko; Ochi, Yukari; Katsuura, Goro; Yamashita, Yui; Ebihara, Ken; Noguchi, Michio; Fujikura, Junji; Taura, Daisuke; Sone, Masakatsu; Hosoda, Kiminori; Gottschall, Paul E.; Nakao, Kazuwa.

In: Neuropeptides, Vol. 65, 01.10.2017, p. 10-20.

Research output: Contribution to journalArticle

Goto, N, Ochi, Y, Katsuura, G, Yamashita, Y, Ebihara, K, Noguchi, M, Fujikura, J, Taura, D, Sone, M, Hosoda, K, Gottschall, PE & Nakao, K 2017, 'Neuronal cells derived from human induced pluripotent stem cells as a functional tool of melanocortin system', Neuropeptides, vol. 65, pp. 10-20. https://doi.org/10.1016/j.npep.2017.04.004
Goto, Nobuko ; Ochi, Yukari ; Katsuura, Goro ; Yamashita, Yui ; Ebihara, Ken ; Noguchi, Michio ; Fujikura, Junji ; Taura, Daisuke ; Sone, Masakatsu ; Hosoda, Kiminori ; Gottschall, Paul E. ; Nakao, Kazuwa. / Neuronal cells derived from human induced pluripotent stem cells as a functional tool of melanocortin system. In: Neuropeptides. 2017 ; Vol. 65. pp. 10-20.
@article{c7af7546d435412a84bc8343ae31079c,
title = "Neuronal cells derived from human induced pluripotent stem cells as a functional tool of melanocortin system",
abstract = "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.",
keywords = "cAMP, Food intake, Human iPS cells, Melanocortin system, Neuronal cells, Neuropeptides",
author = "Nobuko Goto and Yukari Ochi and Goro Katsuura and Yui Yamashita and Ken Ebihara and Michio Noguchi and Junji Fujikura and Daisuke Taura and Masakatsu Sone and Kiminori Hosoda and Gottschall, {Paul E.} and Kazuwa Nakao",
year = "2017",
month = "10",
day = "1",
doi = "10.1016/j.npep.2017.04.004",
language = "English",
volume = "65",
pages = "10--20",
journal = "Neuropeptides",
issn = "0143-4179",
publisher = "Churchill Livingstone",

}

TY - JOUR

T1 - Neuronal cells derived from human induced pluripotent stem cells as a functional tool of melanocortin system

AU - Goto, Nobuko

AU - Ochi, Yukari

AU - Katsuura, Goro

AU - Yamashita, Yui

AU - Ebihara, Ken

AU - Noguchi, Michio

AU - Fujikura, Junji

AU - Taura, Daisuke

AU - Sone, Masakatsu

AU - Hosoda, Kiminori

AU - Gottschall, Paul E.

AU - Nakao, Kazuwa

PY - 2017/10/1

Y1 - 2017/10/1

N2 - 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.

AB - 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.

KW - cAMP

KW - Food intake

KW - Human iPS cells

KW - Melanocortin system

KW - Neuronal cells

KW - Neuropeptides

UR - http://www.scopus.com/inward/record.url?scp=85018648672&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85018648672&partnerID=8YFLogxK

U2 - 10.1016/j.npep.2017.04.004

DO - 10.1016/j.npep.2017.04.004

M3 - Article

VL - 65

SP - 10

EP - 20

JO - Neuropeptides

JF - Neuropeptides

SN - 0143-4179

ER -