Congenital pituitary hypoplasia modeling using induced pluripotent cells
| Project/Area Number |
16H05332
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Endocrinology
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| Research Institution | Kobe University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
長谷川 奉延 慶應義塾大学, 医学部(信濃町), 教授 (20189533)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2018: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2016: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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| Keywords | 疾患iPS細胞 / 下垂体 / 先天性下垂体形成不全 / 下垂体機能低下症 / 疾患特異的iPS細胞 / 遺伝子異常 / iPS細胞 / 下垂体疾患モデル / 病態モデル / 下垂体疾患 |
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| Outline of Final Research Achievements |
Anterior pituitary develops from oral ectoderm in contact with adjacent neural ectoderm that differentiates into hypothalamus with a close interaction. Here, we demonstrate iPSC-based disease modeling for congenital pituitary hypoplasia and investigated its underlying mechanisms. Using exome analysis in a patient with combined pituitary hormone deficiency, we identified a novel OTX2 mutation, of which gene product showed impaired nuclear translocation. The differentiation into pituitary in the patient-derived iPSCs (OTX2mut-iPSCs) was severely impaired. As the underlying mechanisms, the expression of an essential transcription factor for pituitary development, was diminished in OTX2mut-iPSCs. Interestingly, addition of the growth factor to the media restored the expression of transcription factor, indicating that OTX2-dependent expression of growth factor in the hypothalamus plays an important role in the pituitary differentiation.
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| Academic Significance and Societal Importance of the Research Achievements |
先天性下垂体形成不全は小児下垂体機能低下症の中で比較的頻度が高く重症化しうる疾患であるが、その原因、病態は十分に明らかになっていない。本研究では、エクソーム解析による網羅的な解析に加えて疾患特異的iPS細胞を用いたin vitroモデルによる病態解析によりその原因を明らかにすることを目的として行なった。今回疾患iPS細胞が下垂体疾患に応用可能であることを世界で初めて示しただけではなく、これまでのノックアウトマウスでは明らかにしえなかった詳細な機序の解明に繋がるとともに、表現型をレスキューする方法を見出したことから、最終的には治療応用も期待される。
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Report
(4 results)
Research Products
(53 results)
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[Journal Article] Multiple salivary cortisol measurements are a useful tool to optimize metyrapone treatment in patients with Cushing’s syndromes treatment; case presentations.2018
Author(s)
Yoshida K, Fukuoka H, Odake Y, Nakajima S, Tachibana M, Ito J, Hosokawa Y, Yamada T, Miura H, Suematsu N, Matsumoto R, Bando H, Suda K, Nishizawa H, Iguchi G, Ogawa W, Takahashi Y
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Journal Title
Front Endocrinol
Volume: 8
Pages: 375-375
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Factors correlated with serum insulin-like growth factor-I levels in health check-up subjects.2018
Author(s)
Matsumoto R, Koga M, Kasayama S, Fukuoka H, Iguchi G, Odake Y, Yoshida K, BandoH, Suda K, Nishizawa H, Takahashi M, Ogawa W, Takahashi Y
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Journal Title
Growth Horm IGF Res.
Volume: in press
Pages: 55-60
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] A novel thymoma-associated autoimmune disease: Anti-PIT-1 antibody syndrome.2017
Author(s)
Bando H, Iguchi G, Okimura Y, Odake Y, Yoshida K, Matsumoto R, Suda K, Nishizawa H, Fukuoka H, Mokubo A, Tojo K, Maniwa Y, Ogawa W, Takahashi Y.
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Journal Title
Sci Rep.
Volume: 20
Issue: 1
Pages: 43060-43067
DOI
NAID
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] The influence of type 2 diabetes on serum GH and IGF-I levels in hospitalized Japanese patients.2016
Author(s)
Suda K, Matsumoto R, Fukuoka H, Iguchi G, Hirota Y, Nishizawa H, Bando H, Yoshida K, Odake Y, Takahasi M, Sakaguchi K, Ogawa W, Takahashi Y
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Journal Title
Growth Hormone and IGF-I Research.
Volume: 印刷中
Pages: 4-10
DOI
Related Report
Peer Reviewed
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[Journal Article] Genetic and clinical characteristics of Japanese patients with sporadic somatotropinoma2016
Author(s)
Matsumoto R, Izawa M, Fukuoka H, Iguchi G, Odake Y, Yoshida K, Bando H, Suda K, Nishizawa H, Takahashi M, Yamada S, Ogawa W, Takahashi Y.
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Journal Title
Endocrine Journal
Volume: 63
Issue: 11
Pages: 953-963
DOI
NAID
ISSN
0918-8959, 1348-4540
Related Report
Peer Reviewed / Open Access
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[Journal Article] IGF-I induces senescence of hepatic stellate cells and limits fibrosis in a p53-dependent manner.2016
Author(s)
Nishizawa H, Iguchi G, Fukuoka H, Takahashi M, Suda K, Bando H, Matsumoto R, Yoshida K, Odake Y, Ogawa W, Takahashi Y※ IGF-I induces senescence of hepatic stellate cells and limits fibrosis in a p53-dependent manner.
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Journal Title
Sci Rep.
Volume: 6
Issue: 1
Pages: 34605-34605
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Book] 内科学書2018
Author(s)
高橋 裕
Total Pages
3000
Publisher
中山書店
ISBN
9784521737751
Related Report
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[Book] 新臨床内科学2018
Author(s)
高橋 裕
Total Pages
1882
Publisher
医学書院
ISBN
4260102524
Related Report
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