Analysis of the cooperation between transcription activity and lipid metabolism in direct reprogramming
| Project/Area Number |
16K08592
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
鈴木 淳史 九州大学, 生体防御医学研究所, 教授 (30415195)
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| Research Collaborator |
NAKAYAMA Takahiro
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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 |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | ダイレクトリプログラミング / 転写因子 / 代謝 / 脂肪酸 / ベータ酸化 / 肝細胞 / 転写 / クロマチン / 脂質代謝 / 肝細胞様細胞 / アセチル化 / ヒストン修飾 / 転写制御 / アセチルCoA / ベータ酸化 / 核内局在 / Foxa / エピゲノム |
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| Outline of Final Research Achievements |
The strategy of direct cell-fate conversion from one cell type into another cell type, termed “direct reprogramming”, is expected to be a complementary or alternative technology for future cell-based regenerative therapies using pluripotent stem cells. Although transduction of defined sets of transcription factors converts the cell-fate easily and efficiently, most of the parts of the molecular mechanism are still unclear. We performed proteomic analysis to discover interacting partners of a transcription factor, Foxa, which has been used in the direct reprogramming of induced hepatocyte-like (iHep) cells, and found that a considerable number of beta-oxidation enzymes physically associated with the Foxa. As a result of detailed study, we identified that some the beta-oxidation enzymes co-localized and formed a complex with the Foxa in the nucleus of iHep cells. This result suggests novel cooperation between transcriptional regulation and lipid metabolism.
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| Academic Significance and Societal Importance of the Research Achievements |
ダイレクトリプログラミングは、iPS細胞のように未分化状態を経ることがないため、誘導した細胞を患者に移植しても癌化の危険性が低く、また比較的短時間で細胞が誘導可能であるという利点がある。そのため再生医療にとって有効な技術であると目されているが、リプログラミングの機構には不明な部分が多く、誘導効率が高くないという問題がある。本研究成果はそのメカニズムの一旦を明らかにするものであり、安全かつ安定的、そして高効率なリプログラミング技術の確立に貢献するものと考えている。
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Report
(4 results)
Research Products
(3 results)
