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 activi...
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| Veröffentlicht in: | Neuropeptides (Edinburgh) 2017-10, Vol.65, p.10-20 |
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| creator | Yamada-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 |
| description | 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. |
| doi_str_mv | 10.1016/j.npep.2017.04.004 |
| format | Article |
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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.</description><identifier>ISSN: 0143-4179</identifier><identifier>EISSN: 1532-2785</identifier><identifier>DOI: 10.1016/j.npep.2017.04.004</identifier><identifier>PMID: 28434791</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Adult ; Advanced Basic Science ; Agouti-related protein ; Calbindin ; cAMP ; Cell culture ; Cell Differentiation ; Cells, Cultured ; Drug development ; Endocrinology & Metabolism ; Female ; Food intake ; Gene expression ; Glutamic acid receptors ; Hormones ; Human iPS cells ; Humans ; Hypothalamus ; Induced Pluripotent Stem Cells - metabolism ; Melanocortin ; Melanocortin MC4 receptors ; Melanocortin system ; Melanocortins - metabolism ; Melanocyte-stimulating hormone ; Microtubule-associated protein 2 ; mRNA ; N-Methyl-D-aspartic acid receptors ; Neuronal cells ; Neurons ; Neurons - metabolism ; Neuropeptides ; Pluripotency ; Postsynaptic density ; Protein Subunits - metabolism ; Receptors, GABA - metabolism ; Receptors, N-Methyl-D-Aspartate - metabolism ; RNA, Messenger - metabolism ; Stem cells ; Synaptophysin ; Tubulin ; γ-Aminobutyric acid A receptors</subject><ispartof>Neuropeptides (Edinburgh), 2017-10, Vol.65, p.10-20</ispartof><rights>2017 Elsevier Ltd</rights><rights>Copyright © 2017 Elsevier Ltd. All rights reserved.</rights><rights>Copyright Elsevier Science Ltd. Oct 2017</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c439t-cd53601e64294ae9defec3e937de7c87a25f68483247036771c02991ac573b243</citedby><cites>FETCH-LOGICAL-c439t-cd53601e64294ae9defec3e937de7c87a25f68483247036771c02991ac573b243</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.npep.2017.04.004$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28434791$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yamada-Goto, Nobuko</creatorcontrib><creatorcontrib>Ochi, Yukari</creatorcontrib><creatorcontrib>Katsuura, Goro</creatorcontrib><creatorcontrib>Yamashita, Yui</creatorcontrib><creatorcontrib>Ebihara, Ken</creatorcontrib><creatorcontrib>Noguchi, Michio</creatorcontrib><creatorcontrib>Fujikura, Junji</creatorcontrib><creatorcontrib>Taura, Daisuke</creatorcontrib><creatorcontrib>Sone, Masakatsu</creatorcontrib><creatorcontrib>Hosoda, Kiminori</creatorcontrib><creatorcontrib>Gottschall, Paul E</creatorcontrib><creatorcontrib>Nakao, Kazuwa</creatorcontrib><title>Neuronal cells derived from human induced pluripotent stem cells as a functional tool of melanocortin system</title><title>Neuropeptides (Edinburgh)</title><addtitle>Neuropeptides</addtitle><description>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.</description><subject>Adult</subject><subject>Advanced Basic Science</subject><subject>Agouti-related protein</subject><subject>Calbindin</subject><subject>cAMP</subject><subject>Cell culture</subject><subject>Cell Differentiation</subject><subject>Cells, Cultured</subject><subject>Drug development</subject><subject>Endocrinology & Metabolism</subject><subject>Female</subject><subject>Food intake</subject><subject>Gene expression</subject><subject>Glutamic acid receptors</subject><subject>Hormones</subject><subject>Human iPS cells</subject><subject>Humans</subject><subject>Hypothalamus</subject><subject>Induced Pluripotent Stem Cells - metabolism</subject><subject>Melanocortin</subject><subject>Melanocortin MC4 receptors</subject><subject>Melanocortin system</subject><subject>Melanocortins - metabolism</subject><subject>Melanocyte-stimulating hormone</subject><subject>Microtubule-associated protein 2</subject><subject>mRNA</subject><subject>N-Methyl-D-aspartic acid receptors</subject><subject>Neuronal cells</subject><subject>Neurons</subject><subject>Neurons - metabolism</subject><subject>Neuropeptides</subject><subject>Pluripotency</subject><subject>Postsynaptic density</subject><subject>Protein Subunits - metabolism</subject><subject>Receptors, GABA - metabolism</subject><subject>Receptors, N-Methyl-D-Aspartate - metabolism</subject><subject>RNA, Messenger - metabolism</subject><subject>Stem cells</subject><subject>Synaptophysin</subject><subject>Tubulin</subject><subject>γ-Aminobutyric acid A receptors</subject><issn>0143-4179</issn><issn>1532-2785</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kk1rFTEYhYMo9lr9Ay4k4MbNTPM1yQyIIMWPQmkX6jqkmXcw10wyJpPC_fdmvNcuuhACgfCcQ95zXoReU9JSQuXFvg0LLC0jVLVEtISIJ2hHO84apvruKdoRKngjqBrO0Iuc96QSrO-fozPWCy7UQHfI30BJMRiPLXif8QjJ3cOIpxRn_LPMJmAXxmLr0-JLcktcIaw4rzCfFKYePJVgV_fXZ43R4zjhGbwJ0ca0uoDzYVO8RM8m4zO8Ot3n6MfnT98vvzbXt1-uLj9eN1bwYW3s2HFJKEjBBmFgGGECy2HgagRle2VYN8le9JwJRbhUilrChoEa2yl-xwQ_R--OvkuKvwvkVc8ub781AWLJmvYDFZ2sAVT07SN0H0uqc2TNKJNdJ2S3UexI2RRzTjDpJbnZpIOmRG9d6L3eutBbF5oIXZOuojcn63I3w_gg-Rd-Bd4fAahZ3DtIOlsHoWbtEthVj9H93__DI7n1Ljhr_C84QH6Yg-rMNNHftm3YloFKTqoP538A4Z-vnw</recordid><startdate>20171001</startdate><enddate>20171001</enddate><creator>Yamada-Goto, Nobuko</creator><creator>Ochi, Yukari</creator><creator>Katsuura, Goro</creator><creator>Yamashita, Yui</creator><creator>Ebihara, Ken</creator><creator>Noguchi, Michio</creator><creator>Fujikura, Junji</creator><creator>Taura, Daisuke</creator><creator>Sone, Masakatsu</creator><creator>Hosoda, Kiminori</creator><creator>Gottschall, Paul E</creator><creator>Nakao, Kazuwa</creator><general>Elsevier Ltd</general><general>Elsevier Science Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20171001</creationdate><title>Neuronal cells derived from human induced pluripotent stem cells as a functional tool of melanocortin system</title><author>Yamada-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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c439t-cd53601e64294ae9defec3e937de7c87a25f68483247036771c02991ac573b243</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adult</topic><topic>Advanced Basic Science</topic><topic>Agouti-related protein</topic><topic>Calbindin</topic><topic>cAMP</topic><topic>Cell culture</topic><topic>Cell Differentiation</topic><topic>Cells, Cultured</topic><topic>Drug development</topic><topic>Endocrinology & Metabolism</topic><topic>Female</topic><topic>Food intake</topic><topic>Gene expression</topic><topic>Glutamic acid receptors</topic><topic>Hormones</topic><topic>Human iPS cells</topic><topic>Humans</topic><topic>Hypothalamus</topic><topic>Induced Pluripotent Stem Cells - metabolism</topic><topic>Melanocortin</topic><topic>Melanocortin MC4 receptors</topic><topic>Melanocortin system</topic><topic>Melanocortins - metabolism</topic><topic>Melanocyte-stimulating hormone</topic><topic>Microtubule-associated protein 2</topic><topic>mRNA</topic><topic>N-Methyl-D-aspartic acid receptors</topic><topic>Neuronal cells</topic><topic>Neurons</topic><topic>Neurons - metabolism</topic><topic>Neuropeptides</topic><topic>Pluripotency</topic><topic>Postsynaptic density</topic><topic>Protein Subunits - metabolism</topic><topic>Receptors, GABA - metabolism</topic><topic>Receptors, N-Methyl-D-Aspartate - metabolism</topic><topic>RNA, Messenger - metabolism</topic><topic>Stem cells</topic><topic>Synaptophysin</topic><topic>Tubulin</topic><topic>γ-Aminobutyric acid A receptors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yamada-Goto, Nobuko</creatorcontrib><creatorcontrib>Ochi, Yukari</creatorcontrib><creatorcontrib>Katsuura, Goro</creatorcontrib><creatorcontrib>Yamashita, Yui</creatorcontrib><creatorcontrib>Ebihara, Ken</creatorcontrib><creatorcontrib>Noguchi, Michio</creatorcontrib><creatorcontrib>Fujikura, Junji</creatorcontrib><creatorcontrib>Taura, Daisuke</creatorcontrib><creatorcontrib>Sone, Masakatsu</creatorcontrib><creatorcontrib>Hosoda, Kiminori</creatorcontrib><creatorcontrib>Gottschall, Paul E</creatorcontrib><creatorcontrib>Nakao, Kazuwa</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Neuropeptides (Edinburgh)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yamada-Goto, Nobuko</au><au>Ochi, Yukari</au><au>Katsuura, Goro</au><au>Yamashita, Yui</au><au>Ebihara, Ken</au><au>Noguchi, Michio</au><au>Fujikura, Junji</au><au>Taura, Daisuke</au><au>Sone, Masakatsu</au><au>Hosoda, Kiminori</au><au>Gottschall, Paul E</au><au>Nakao, Kazuwa</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Neuronal cells derived from human induced pluripotent stem cells as a functional tool of melanocortin system</atitle><jtitle>Neuropeptides (Edinburgh)</jtitle><addtitle>Neuropeptides</addtitle><date>2017-10-01</date><risdate>2017</risdate><volume>65</volume><spage>10</spage><epage>20</epage><pages>10-20</pages><issn>0143-4179</issn><eissn>1532-2785</eissn><abstract>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.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>28434791</pmid><doi>10.1016/j.npep.2017.04.004</doi><tpages>11</tpages></addata></record> |
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| subjects | Adult Advanced Basic Science Agouti-related protein Calbindin cAMP Cell culture Cell Differentiation Cells, Cultured Drug development Endocrinology & Metabolism Female Food intake Gene expression Glutamic acid receptors Hormones Human iPS cells Humans Hypothalamus Induced Pluripotent Stem Cells - metabolism Melanocortin Melanocortin MC4 receptors Melanocortin system Melanocortins - metabolism Melanocyte-stimulating hormone Microtubule-associated protein 2 mRNA N-Methyl-D-aspartic acid receptors Neuronal cells Neurons Neurons - metabolism Neuropeptides Pluripotency Postsynaptic density Protein Subunits - metabolism Receptors, GABA - metabolism Receptors, N-Methyl-D-Aspartate - metabolism RNA, Messenger - metabolism Stem cells Synaptophysin Tubulin γ-Aminobutyric acid A receptors |
| title | Neuronal cells derived from human induced pluripotent stem cells as a functional tool of melanocortin system |
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