Activation mechanisms of skeletal muscle stem cells during regeneration
| Project/Area Number |
16H04793
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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 |
Developmental biology
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| Research Institution | Kyoto University |
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Principal Investigator |
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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 |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2018: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2017: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2016: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
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| Keywords | 再生医学 / 細胞・組織 / 発生・分化 / 生体分子 / ゲノム |
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| Outline of Final Research Achievements |
We investigated factors stimulating differentiation of skeletal muscle satellite cells (SMSCs), and found that pyruvate, the end product of glycolysis, stimulates their differentiation. Pyruvate antagonizes effects of hypoxia on preferential self-renewal of SMSCs through dephosphorylation or activation of pyruvate dehydrogenase (PDH), which mediates opening of the gateway from glycolysis to tricarboxylic acid (TCA) cycle by producing acetyl coA from pyruvate. PDH kinase 1 is decreased under normoxic conditions, leading to an increase in dephosphorylated PDH. Conditional deletion of PDH in SMSCs affects cell divisions generating myocytes and subsequent myotube formation skeletal muscle regeneration upon injury, and aggravated pathogenesis of dystrophin-deficient mice. Thus, the metabolic flow from glycolysis to TCA cycle mediated by PDH plays a pivotal role in the efficient differentiation of SMSCs, which is critical for the progression of skeletal muscle regeneration.
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| Academic Significance and Societal Importance of the Research Achievements |
幹細胞がどのようなメカニズムで活性化され、増殖・分化するのか、という問題については、幹細胞研究が盛んな割にはわかっていない。その中にあって、最も基本的なエネルギー利用の観点から、糖代謝の変化が骨格筋幹細胞の分化に必要ということを、細胞レベル・個体レベルで示すことができ、学術的にも、医学応用的にも、非常に重要な知見を生み出すことができた。
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Report
(4 results)
Research Products
(46 results)
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[Presentation] 人工重力発生装置を用いたゼブラフィッシュ宇宙滞在実験2018
Author(s)
佐藤文規, Choi Minyong, 王梓, 今村聖実, 堀内映美, 呉泉, 藤田生水, 内田智子, 加藤充康, 谷垣文章, 東端晃, 村谷匡史, 小林純也, 高橋昭久, 菅野純夫, 松崎文雄, 鈴木穣, 川上浩一, 瀬原淳子
Organizer
宇宙生物科学会第32回大会
Related Report
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[Presentation] Study on gravity-dependent skeletal muscle maintenance mechanisms using Zebrafish, aquatic organisms2018
Author(s)
Fuminori Sato, Minyong Choi, Zi Wang, Kiyomi Imamura, Terumi Horiuchi, Wu Quan, Ikumi Fujita, Satoko Uchida, Mitsuyasu Kato, Fumiaki Tanigaki, Akira Higashibata, Masafumi Muratani, Junya Kobayashi, Akihisa Takahashi, Sumio Sugano, Fumio Matsuzaki, Yutaka Suzuki, Koichi Kawakami, Atsuko Sehara-Fujisawa
Organizer
2018 ASCB EMBO Meeting
Related Report
Int'l Joint Research
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[Presentation] Studies on skeletal muscle atrophy in space-what zebrafish experienced in a space tour2018
Author(s)
Uchida, Toru Sakimura, Yasushi Kono, Masaki Shirakawa, Fumiaki Tanigaki, Masahiro Chatani, Akira Kudo, Akihisa Takahashi, Junya Kobayashi, Kiyomi Imamura, Terumi Horiuchi, Satoshi Furukawa, Tadashi Muratani, Sumio Sugano, Yutaka Suzuki, Fumio Matsuzaki, Koichi Kawakami, and Atsuko Sehara-Fujisawa
Organizer
CDB Symposium 2018
Related Report
Int'l Joint Research
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