Single cell profiling of GI cancer-initiating cells and their niche
| Project/Area Number |
20H03656
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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 53010:Gastroenterology-related
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Hayakawa Yoku 東京大学, 医学部附属病院, 講師 (60777655)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2022: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2021: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2020: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
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| Keywords | 胃癌 / 腫瘍微小環境 / 胃上皮幹細胞 / 消化管幹細胞 / 幹細胞ニッチ / 消化管癌 |
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| Outline of Research at the Start |
消化管粘膜増殖帯に存在する幹細胞群、もしくは一部の成熟細胞群がどのように癌起源細胞へと変質し、また増殖・浸潤・転移能を獲得していくのかを、周囲の微小環境とともに時系列的に可視化し、また単一細胞レベルの転写・免疫プロファイリングによってその分子学的機序を解析し、消化管癌の発生進展メカニズムを考察する。
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| Outline of Final Research Achievements |
In this study, we molecularly examined the proliferation and expansion of gastric cancer-originating cells and the progression of cancer cells using mouse models and omics-analysis including single-cell level analysis and spatial analysis. Lineage tracing experiments revealed that epithelial stem cells are the main source of gastric cancer, and that dedifferentiation from mature differentiated cells such as chief cells hardly contributes to gastric cancer. Genetically engineered mice and single cell analysis showed that Rspo3/Lgr4 signals are important for proliferation and differentiation of stem cells. Investigation of a genetically modified model that develops gastric cancer revealed that gene mutations in tumor cells lead to high expression of characteristic molecules, which in turn causes remodeling of the surrounding microenvironment.
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| Academic Significance and Societal Importance of the Research Achievements |
胃癌発生段階における癌起源細胞とその周囲微小環境の変化の詳細解析により、胃発癌の分子学的メカニズムの一端が明らかになった。癌起源細胞とその周囲微小環境の変化を独自の遺伝子改変マウスの解析により、前癌病変・早期癌・浸潤癌・転移性癌の分子学的相違を明らかとなり、癌進行度別・サブタイプ別の病態理解が促進された。本解析によって得られたデータは、癌の予防および治療戦略を構築する上で極めて重要な新規創薬シーズとなると考えられる。
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Report
(4 results)
Research Products
(15 results)
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[Journal Article] Helicobacter pylori CagA elicits BRCAness to induce genome instability that may underlie bacterial gastric carcinogenesis2021
Author(s)
S Imai, T Ooki, N Murata-Kamiya, D Komura, K Tahmina, W Wu, Atsushi Takahashi-Kanemitsu, C T Knight, A Kunita, N Suzuki, A Del Valle, M Tsuboi, M Hata, Y Hayakawa, N Ohnishi, K Ueda, M Fukayama, T Ushiku, S Ishikawa, M Hatakeyama
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Journal Title
Cell Host & Microbe
Volume: 29
Issue: 6
Pages: 1-18
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Dysregulated Immune Responses by ASK1 Deficiency Alter Epithelial Progenitor Cell Fate and Accelerate Metaplasia Development during H. pylori Infection.2020
Author(s)
Hayakawa, Y.; Hirata, Y.; Hata, M.; Tsuboi, M.; Oya, Y.; Kurokawa, K.; Abe, S.; Arai, J.; Suzuki, N.; Nakagawa, H.; Fujiwara, H.; Tateishi, K.; Maeda, S.; Koike, K
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Journal Title
Microorganisms
Volume: 8
Issue: 12
Pages: 1-20
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] GRP30-expressing gastric chief cells do not differentiate but are eliminated via PDK-dependent cell competition during development of metaplasia.2020
Author(s)
1.Hata M, Kinoshita H, Hayakawa Y, Konishi M, Tsuboi M, Oya Y, Hayata Y, Nakagawa H, Tateishi K, Fujiwara H, Hirata Y, Worthley DL, Muranishi Y, Furukawa T, Kon S, Tomita H, Wang TC, Koike K.
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Journal Title
Gastroenterology
Volume: 158
Issue: 6
Pages: 1650-1666
DOI
Related Report
Peer Reviewed / Int'l Joint Research
