Chemical screening for steroidogenic differentiation of human iPSC-derived intermediate mesoderm cells.
Project/Area Number |
26461380
|
Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Endocrinology
|
Research Institution | Kyoto University |
Principal Investigator |
SONE Masakatsu 京都大学, 医学研究科, 特定准教授 (40437207)
|
Co-Investigator(Kenkyū-buntansha) |
田浦 大輔 京都大学, 医学研究科, 特定助教 (10558612)
|
Research Collaborator |
OSAFUNE Kenji
|
Project Period (FY) |
2014-04-01 – 2017-03-31
|
Project Status |
Completed (Fiscal Year 2016)
|
Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
Keywords | ステロイドホルモン / 副腎皮質 / 性腺 / 発生分化 / 内分泌 / ステロイド / 再生 / 内分泌学 |
Outline of Final Research Achievements |
We tried to elucidate the steroidogenic differentiation processes using hiPSC-derived intermediate mesoderm (IM) that is known to be the origin of the human adrenal cortex and gonads. We first performed chemical screening to identify small molecules that induce steroidogenic differentiation of IM cells expressing OSR1, an early IM marker. We identified cabergoline as an inducer of 3β-HSD2, an essential enzyme for steroidogenesis. Although cabergoline is a potent dopamine D2 receptor agonist, additional experiments showed that cabergoline exerted effects as a low-affinity agonist of D1 receptors. Further analysis of OSR1+ cells transfected with SF-1/Ad4BP revealed that D1 receptor agonist upregulated expression of various steroidogenic enzymes and increased secretion of steroid hormones. These results suggest the importance of dopamine D1 receptor signalling in steroidogenic differentiation, which contributes to effective induction of steroidogenic cells from hiPSCs.
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Report
(4 results)
Research Products
(11 results)
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[Journal Article] Endothelium-Derived C-Type Natriuretic Peptide Contributes to Blood Pressure Regulation by Maintaining Endothelial Integrity.2017
Author(s)
Nakao K, Kuwahara K, Nishikimi T, Nakagawa Y, Kinoshita H, Minami T, Kuwabara Y, Yamada C, Yamada Y, Tokudome T, Nagai-Okatani C, Minamino N, Nakao YM, Yasuno S, Ueshima K, Sone M, Kimura T, Kangawa K, Nakao K.
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Journal Title
Hypertension.
Volume: 69(2)
Pages: 286-296.
DOI
Related Report
Peer Reviewed
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[Journal Article] Crucial Role of Mesangial Cell-derived Connective Tissue Growth Factor in a Mouse Model of Anti-Glomerular Basement Membrane Glomerulonephritis.2017
Author(s)
Toda N, Mori K, Kasahara M, Ishii A, Koga K, Ohno S, Mori KP, Kato Y, Osaki K, Kuwabara T, Kojima K, Taura D, Sone M, Matsusaka T, Nakao K, Mukoyama M, Yanagita M, Yokoi H.
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Journal Title
Sci Rep.
Volume: 7
Pages: 42114.
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Overall safety and efficacy of high-dose and low-dose intravenous glucocorticoid therapy in patients with moderate-to-severe active Graves' ophthalmopathy.2016
Author(s)
Ueda-Sakane Y, Kanamoto N, Fushimi Y, Tanaka-Mizuno S, Yasuno S, Miura M, Sone M, Yasoda A, Okada T, Togashi K, Nakao K, Inagaki N
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Journal Title
Endocr J.
Volume: 63(8)
Pages: 703-14
DOI
Related Report
Peer Reviewed
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[Journal Article] Transcriptional Analysis of Intravenous Immunoglobulin Resistance in Kawasaki Disease Using an Induced Pluripotent Stem Cell Disease Model.2016
Author(s)
Ikeda K, Mizoro Y, Ameku T, Nomiya Y, Mae SI, Matsui S, Kuchitsu Y, Suzuki C, Hamaoka-Okamoto A, Yahata T, Sone M, Okita K, Watanabe A, Osafune K, Hamaoka K.
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Journal Title
Circ J.
Volume: 81(1)
Pages: 110-118.
DOI
Related Report
Peer Reviewed
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[Journal Article] Impaired adipogenic capacity in induced pluripotent stem cells from lipodystrophic patients with BSCL2 mutations.2016
Author(s)
Mori E, Fujikura J, Noguchi M, Nakao K, Matsubara M, Sone M, Taura D, Kusakabe T, Ebihara K, Tanaka T, Hosoda K, Takahashi K, Asaka I, Inagaki N, Nakao K.
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Journal Title
Metabolism.
Volume: 65(4)
Pages: 543-56.
DOI
Related Report
Peer Reviewed
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