Mechanism for the differentiation of skeletal muscle satellite cells into adipose cell lineage and stability of cell differentiation
| Project/Area Number |
15580250
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Applied animal science
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| Research Institution | Meiji University |
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Principal Investigator |
MARUYAMA Kimiaki Meiji University, Faculty of Agriculture, Professor, 農学部, 教授 (80328971)
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| Co-Investigator(Kenkyū-buntansha) |
ONO Yoshitaka Saga Univeristy, Faculty of Agriculture, Associate Professor, 農学部, 助教授 (00112318)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | skeletal muscle satellite cells / adult stem cells / myogenic cells / adipose cells / cattle / pluripotency / differentiation / 衛星細胞 / 成体幹細胞 |
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| Research Abstract |
The mechanism of cell differentiation was investigated using skeletal muscle satellite cells (satellite cells). Traditionally, satellite cells are regarded as the precursor cells for muscle cells and their differentiation was limited only to the myogenic lineage. However, in this investigation, the traditional concept was put to the reexamination and the plasticity of cell differentiation was proved. When satellite cells were icultured as were myogenic cells, they underwent the proliferation and differentiation to form myotubes, which was irreversible terminal myogenic differentiation. When satellite cells were transfected with PPARγ and then, cultured as were myogenic cells, the accumulation of lipid droplets were observed, even among myotubes. This induction of adipogenic lineage was also induced by the use of culture media containing insulin, dexamethasone and IBMX in the medium. When this occurred, there was reduction in the expression of MyoD, which is one of myogenic regulatory factor genes. Therefore, it was concluded that differentiation is not an irreversible process to determine the fate of cells and the decision for the cell lineage was made by the expression, rather relative expression intensity, of lineage specific master genes. From the results, the reduction in the expression of lineage-determination genes was regulated by silencing rather than inactivation of these genes. In fact, during the myogenic differentiation, the rise of MyoD expression coincided with the fall of PPAR γ expression while maintaining the ability to function as adipose cells. Since myogenic regulatory genes are transactivating each other, the identification of "Lineage-determination master genes" was conducted by determining the transactivation hierarchy among four Myogenic regulatory genes. From siRNA experiments, it was concluded that MRF4 was most upstream, hence, it was a tentative lineage-determination master gene.
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Report
(3 results)
Research Products
(1 results)
