Establishment of iPSCs and osteoblast differentiation of fibroblasts from Go rlin syndrome patients.
| Project/Area Number |
15K20379
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Functional basic dentistry
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| Research Institution | Tokyo Dental College |
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Principal Investigator |
Shino Hiromi 東京歯科大学, 歯学部, 助教 (00445446)
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 疾患特異的iPS細胞 / iPS細胞 / 骨芽細胞 / 骨細胞 / Hedgehog |
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| Outline of Final Research Achievements |
Disease-specific pluripotent stem cells (iPSCs) allow in vitro investigation of genetic diseases with unclear phenotype－genotype associations, such as Gorlin syndrome. We generated iPSCs from four unrelated Gorlin syndrome patients, all with genetic functional loss of PTCH1, using the SeVdp (KOSM302L) vector. Activation of the Hedgehog (Hh) effector Smoothened (SMO) by SAG plus osteo-induction induced significantly higher ALP expression in patient-derived iPSCs than control iPSC lines. Patient-derived iPSCs had lower basal expression of Hhs, Wnts, and BMPs than control iPSCs before osteogenic induction, but much greater increases under osteogenic treatment, indicating osteogenic hypersensitivity. We propose that iPSCs from Gorlin syndrome patients have constitutively active Hh signaling, which confers enhanced susceptibility to osteogenesis and contributes to disease-associated abnormalities.
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Report
(3 results)
Research Products
(9 results)
