2015 Fiscal Year Final Research Report
Establishment of induced pluripotent stem cells from glycogen storage disease type Ib patient and making disease models
| Project/Area Number |
26670038
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pharmacology in pharmacy
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| Research Institution | Nagoya City University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
ITO Tetsuya 藤田保健衛生大学, 医学部, 教授 (80336677)
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| Co-Investigator(Renkei-kenkyūsha) |
MAEDA Tohru 金城学院大学, 薬学部, 准教授 (90381855)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Keywords | ヒト骨髄性白血病細胞 / 好中球 / 糖原病Ib |
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| Outline of Final Research Achievements |
Glycogen storage disease type Ib (GSD-Ib) is caused by mutations in the glucose-6-phosphate transporter (G6PT) gene, which is involved in glycogen metabolism. Patients with GSD-Ib are known to develop neutropenia as a specific symptom, but the causes remain unclear. We examined the mechanism of reactive oxygen species production after differentiation from HL-60 cells, and the collapse of glycogen metabolism because of G6PT deficiency. A high intracellular glucose level leads to an increase in ROS production by PKC induction.
We established induced pluripotent stem cells (iPS cells) from patients with GSD-Ib. iPS cells-derived hepatocytes generated from patients with GSDIb metabolic abnormalities recapitulated key pathological features of the diseases affecting the patients from whom they were derived, such as glycogen, lactate, pyruvate and lipid accumulation. Cells that were differentiated into neutrophils also showed the GSDIb pathology.
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| Free Research Field |
幹細胞生物学
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