Epigenetic regulation of cardiac progenitor cells development in lateral plate mesoderm/pharyngeal region.
| Project/Area Number |
18H02786
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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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| Review Section |
Basic Section 52050:Embryonic medicine and pediatrics-related
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| Research Institution | National Cardiovascular Center Research Institute |
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Principal Investigator |
Shirai Manabu 国立研究開発法人国立循環器病研究センター, オープンイノベーションセンター, 室長 (70294121)
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| Co-Investigator(Kenkyū-buntansha) |
若林 真樹 国立研究開発法人国立循環器病研究センター, オープンイノベーションセンター, 室長 (70552024)
笹井 紀明 奈良先端科学技術大学院大学, 先端科学技術研究科, 准教授 (80391960)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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| Keywords | 心臓前駆細胞 / エピジェネティック因子 / 先天性心疾患 |
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| Outline of Final Research Achievements |
In the lateral plate mesoderm (LPM) and pharyngeal mesoderm (PM), a part of multipotent mesenchymal cells divides into the cardiac progenitor cells (CPCs). CPCs proliferate, differentiate, and migrate to contribute to the right ventricle and cardiac outflow tract formation. To elucidate the epigenetic regulatory mechanisms for CPCs differentiation, we performed single cell RNA-seq (scRNA-seq) analysis and the proteome analysis. We defined Phc1 positive/Isl1 negative specific cell cluster which is also same with Tbx1 or Tbx2 expressing cell cluster and Phc1 negative/Isl1 positive cell cluster. We also identified many candidate proteins binding with Phc1 in LPM and PM. From these results, we hypothesis a specific crosstalk between the transcriptional network and Polycomb group complex might regulates CPCs differentiation.
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| Academic Significance and Societal Importance of the Research Achievements |
DiGeorge症候群を含む染色体22q11.2欠損症候群（22q11.2DS）は、心臓流出路の先天性疾患を伴った胸部組織（甲状腺、胸腺等）の形成異常を生じる。これらの症状は胎仔鰓弓・側板中胚葉中の心臓前駆細胞の増殖・分化・遊走障害により説明される。本研究においてscRNA-seq解析とプロテオーム解析を組み合わせることにより、心臓前駆細胞の発生を制御する転写因子とエピジェネティック因子間のクロストーク解明への道が開けたばかりでなく、ヒト先天性心疾患の原因及び重症化機構の解明に向けた新たな分子基盤を構築することができた。
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Report
(4 results)
Research Products
(3 results)
