Single-cell omics analysis to develop the therapy for heart failure via cardiomyocyte reprogramming
| Project/Area Number |
19H03649
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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 53020:Cardiology-related
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Nomura Seitaro 東京大学, 医学部附属病院, 特任助教 (10722118)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2021: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2020: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2019: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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| Keywords | 心不全 / シングルセル解析 / 心筋リプログラミング / シングルセル生物学 / ゲノム編集 |
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| Outline of Research at the Start |
心不全は、心臓の中心的な構成要素である心筋細胞の機能的な破綻により生じます。我々は、心臓の中に存在する全ての細胞のシングルセルレベルの全遺伝子発現を解析することで、心不全発症過程において心筋細胞でどのような遺伝子発現のダイナミクスが生じるかを明らかにすることに成功しました。本研究では、この遺伝子発現の情報を基にして、不全型の心筋細胞をリプログラミングして心不全の病態を改善する治療法の開発を目指します。
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| Outline of Final Research Achievements |
By using single-cell RNA-seq analysis, we clarified that cardiomyocytes diverge into adaptive and failing cardiomyocytes in the onset of heart failure, and DNA damage and activation of p53 signaling are important in the induction of failing cardiomyocytes. Next, by extracting cell-cell interactions from single-cell data, we revealed that the interplay of TGF-beta signaling between cardiac fibroblasts and cardiomyocytes induces cardiomyocyte senescence. By integrating spatial transcriptome and single-cell RNA-seq of the post-myocardial infarction heart, we identified mechanosensing gene-positive cardiomyocytes that appear at the border zone of myocardial infarction, and revealed that they adaptively regulate the formation of cardiac remodeling.
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| Academic Significance and Societal Importance of the Research Achievements |
心不全は、心臓のポンプ機能の低下によって全身に十分な量の血液を送れなくなる病態であり、がんと並んで世界中で多くの患者の命を脅かしています。これまで心不全がなぜ起こるのかわからない点が多かったのですが、我々は心臓を構成する細胞を取り出してそれぞれの細胞に含まれる全ての遺伝子を読み取る技術を確立してその疑問を明らかにすることができました。今後は、この研究で明らかになった心不全のメカニズムに基づいた新しい治療法を開発していきます。
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Report
(4 results)
Research Products
(78 results)
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[Journal Article] Functional Evaluation of Human Bioengineered Cardiac Tissue Using iPS Cells Derived from a Patient with Lamin Variant Dilated Cardiomyopathy2022
Author(s)
Miura K, Matsuura K, Yamasaki Itoyama Y, Sasaki D, Takada T, Furutani Y, Hayama E, Ito M, Nomura S, Morita H, Toyoda M, Umezawa A, Onoue K, Saito Y, Aburatani H, Nakanishi T, Hagiwara N, Komuro I, Shimizu T.
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Journal Title
International Heart Journal
Volume: 63
Issue: 2
Pages: 338-346
DOI
ISSN
1349-2365, 1349-3299
Year and Date
2022-03-30
Related Report
Peer Reviewed / Open Access
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[Journal Article] New Vision, Mission, and Values of the Japanese Circulation Society2021
Author(s)
Ishida M, Matsumoto C, Kida K, Fukuda M, Kagiyama N, Kusunose K, Matsumoto S, Nomura S, Okumura T, Shiono Y, Taniguchi T, Mizuno A, Kishi T, Node K, Komuro I, Hirata KI; Directors of the Japanese Circulation Society.
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Journal Title
Circulation Journal
Volume: 85
Issue: 12
Pages: 2248-2251
DOI
NAID
ISSN
1346-9843, 1347-4820
Year and Date
2021-11-25
Related Report
Peer Reviewed / Open Access
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[Journal Article] Activation of Sympathetic Signaling in Macrophages Blocks Systemic Inflammation and Protects against Renal Ischemia-Reperfusion Injury2021
Author(s)
Hasegawa S, Inoue T, Nakamura Y, Fukaya D, Uni R, Wu CH, Fujii R, Peerapanyasut W, Taguchi A, Kohro T, Yamada S, Katagiri M, Ko T, Nomura S, Nakanishi Ozeki A, Susaki EA, Ueda HR, Akimitsu N, Wada Y, Komuro I, Nangaku M, Inagi R.
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Journal Title
J Am Soc Nephrol.
Volume: -
Issue: 7
Pages: 1599-1615
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Population-specific and trans-ancestry genome-wide analyses identify distinct and shared genetic risk loci for coronary artery disease2020
Author(s)
2.Koyama S, Ito K, Terao C, Akiyama M, Horikoshi M, Momozawa Y, Matsunaga H, Ieki H, Ozaki K, Onouchi Y, Takahashi A, Nomura S, Morita H, Akazawa H, Kim C, Seo JS, Higasa K, Iwasaki M, Yamaji T, et al.
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Journal Title
Nature Genetics
Volume: 52
Issue: 11
Pages: 1169-1177
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Cardiac dopamine D1 receptor triggers ventricular arrhythmia in chronic heart failure2020
Author(s)
Yamaguchi Toshihiro、Sumida Tomokazu S.、Nomura Seitaro、Satoh Masahiro、Higo Tomoaki、Ito Masamichi、Ko Toshiyuki、Fujita Kanna、Sweet Mary E.、Sanbe Atsushi、Yoshimi Kenji、Manabe Ichiro、Sasaoka Toshikuni、Taylor Matthew R. G.、Toko Haruhiro、Takimoto Eiki、Naito Atsuhiko T.、Komuro Issei
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Journal Title
Nature Communications
Volume: 11
Issue: 1
Pages: 4364-4364
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Quantification of DNA Damage in Heart Tissue as a Novel Prediction Tool for Therapeutic Prognosis of Patients With Dilated Cardiomyopathy.2019
Author(s)
Ko T, Fujita K, Nomura S, Uemura Y, Yamada S, Tobita T, Katoh M, Satoh M, Ito M, Domoto Y, Hosoya Y, Amiya E, Hatano M, Morita H, Fukayama M, Aburatani H, Komuro I.
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Journal Title
JACC Basic Transl Sci.
Volume: 4
Issue: 6
Pages: 670-680
DOI
Related Report
Peer Reviewed / Open Access
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