Regulation of hemangioblst development by partial Epithelial Mesenchymal Transition
Project/Area Number |
21H02490
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 44020:Developmental biology-related
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Research Institution | Kumamoto University |
Principal Investigator |
Sheng Guojun 熊本大学, 国際先端医学研究機構, 特別招聘教授 (20399439)
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Co-Investigator(Kenkyū-buntansha) |
永井 宏樹 熊本大学, 国際先端医学研究機構, リサーチ・スペシャリスト (80772508)
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Project Period (FY) |
2021-04-01 – 2024-03-31
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Project Status |
Granted (Fiscal Year 2023)
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Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2023: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2022: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2021: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
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Keywords | EMT / chicken / hemangioblast / hematopoiesis / vasculogenesis / Embryo |
Outline of Research at the Start |
EMT is an important morphogenetic process. Its mis-regulation is associated with cancers. EMT also plays a role in hematopoietic development and disease. In this project, we will use the avian model and investigate the role of partial EMT during primitive hematopoiesis. We will characterize partial epithelial and mesenchymal features of hemangioblasts from stages HH4-10; analyze functional involvement of two EMT transcription factors (Snai2, Zeb2); investigate cross-talk between EMT TFs and hemangioblast TFs in partial EMT regulation and promote blood/vessel specification via EMT modulation.
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Outline of Annual Research Achievements |
In FY2022, we have performed experiments on effect of overexpression of Snai2 and Zeb2 in lineage contribution (blood, vessel, smooth muscle lineages). We have found that these EMT markers do not clearly affect lineage marker gene expression. However, they affect cell lineage segregation, likely after lineage specification. We have also investigated relationship between hemangioblast specifiers (NPAS4L and ETV2, two markers upstream of blood/vessel markers SCL/LMO2 and smooth muscle markers HAND1/2) and EMT regulators. As EMT occurs both before (during mesoderm formation) and after hemagioblast specification and at least SNAI2 is involved in both primitive streak EMT and lateral plate mesoderm EMT (subject of this project), we are in the process of sorting out epistatic relationship between SNAI2, NPAS4L, and SCL/LMO2/HAND2).
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Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
The project is making progress as planned.
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Strategy for Future Research Activity |
In FY2023, we will continue the project with the same direction outlined in our grant application. We will study relationship of EMT regulators (SNAI2 and ZEB2) and cell biological markers, including NCAM, a cell surface markers which we have found to correlated with hemangioblast differentiation, and VE-cadherin, a vascular specific adherens junction molecule marker endothelial type of epithelial organization. We aim to submit the results of this project for publication by the end of this fiscal year.
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Report
(2 results)
Research Products
(14 results)
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[Journal Article] Tumor microenvironmental 15‐PGDH depletion promotes fibrotic tumor formation and angiogenesis in pancreatic cancer2022
Author(s)
Bu L, Yonemura A, Yasuda-Yoshihara N, Uchihara T, Ismagulov G, Takasugi S, Yasuda T, Okamoto Y, Kitamura F, Akiyama T, Arima K, Itoyama R, Zhang J, Fu L, Hu X, Wei, F, Arima Y, Moroishi T, Nishiyama K, Sheng G, Mukunoki T, Otani J, Baba H, Ishimoto T
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Journal Title
Cancer Science
Volume: 113
Issue: 10
Pages: 3579-3592
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] HMGN3 represses transcription of epithelial regulators to promote migration of cholangiocarcinoma in a SNAI2-dependent manner2022
Author(s)
Supannika Sorin, Sho Kubota, Sofiane Hamidi, Takako Yokomizo-Nakano, Kulthida Vaeteewoottacharn, Sopit Wongkham, Sakda Waraasawapati, Chawalit Pairojkul, Jie Bai, Mariko Morii, Guojun Sheng, Kanlayanee Sawanyawisuth, Goro Sashida
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Journal Title
The FASEB Journal
Volume: 36
Issue: 7
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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