Elucidation of molecular mechanism of the robustness between T and B cell lineage
| Project/Area Number |
16K09870
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Kyoto University |
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Principal Investigator |
Masuda Kyoko 京都大学, ウイルス・再生医科学研究所, 助教 (40565777)
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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 |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 系列決定 / 系列頑健性 / ポリコーム遺伝子 / T細胞分化 / ミエロイド細胞 / T前駆細胞 / ポリコーム / Pax5 / B前駆細胞 / 血液免疫学 / T細胞 / B細胞 |
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| Outline of Final Research Achievements |
It has been known that transcription factors play important roles for the determination of cell fate in the process of hematopoiesis. In this study, we tried to figure out how epigenetic mechanism regulate the lineage maintenance and the robustness. The analysis of mice conditionally deleted for polycomb genes in T cell progenitors revealed that T cell development was arrested at DN stage and those cells were converted to B cell lineage. Further, we examined whether non-T lineage cells also were able to be converted to another lineage. When progenitor cells of various lineage from mice conditionally deleted for polycomb gene in hematopoietic cells were cultured in the presence of cytokine cocktail, erythroid, megakaryocyte, B cell and T cell linage progenitors were converted to myeloid lineage. These results indicate that progenitors of all hematopoietic lineages retain latent myeloid potential beyond the lineage decision and their myeloid program is suppressed by polycomb genes.
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| Academic Significance and Societal Importance of the Research Achievements |
細胞の運命決定に転写因子が深く関与することはすでに知られていたが、本研究により、転写因子だけではなくエピジェネティック制御によっても系列決定状態が規定されていることが示された。また全ての血球細胞は、系列が決定されたあとも潜在的にミエロイド細胞への分化能を有していることも示された。これらの結果は、血液細胞が進化の過程において、どのようなプロセスを経て各系列の細胞種を創出してきたか、各系列間での関係性はどのようなものであるかを考える上で非常に重要な知見であり、本研究が血液学をより深く理解するためにもたらした意義は非常に大きいものである。
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Report
(4 results)
Research Products
(16 results)
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[Journal Article] Recurrent SPI1 (PU.1) fusions in high-risk pediatric T cell acute lymphoblastic leukemia.2017
Author(s)
Seki M, Kimura S, Isobe T, Yoshida K, (13 authors), Masuda K, Kawamoto H, Ohki K, Kato M, Arakawa Y, Koh K, Hanada R, Moritake H, Akiyama M, Kobayashi R, Deguchi T, Hashii Y, Imamura T, Sato A, Kiyokawa N, Oka A, Hayashi Y, Takagi M, Manabe A, Ohara A, Horibe K, Sanada M, Iwama A, Mano H, Miyano S, Ogawa S, Takita J
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Journal Title
Nature Genetics
Volume: 49
Issue: 8
Pages: 1274-1281
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] NK Cell Alloreactivity against KIR-Ligand-Mismatched HLA-Haploidentical Tissue Derived from HLA Haplotype-Homozygous iPSCs.2017
Author(s)
Ichise H, Nagano S, Maeda T, Miyazaki M, Miyazaki Y, Kojima H, Yawata N, Yawata M, Tanaka H, Saji H, Masuda K, Kawamoto H
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Journal Title
Stem Cell Reports
Volume: 9
Issue: 3
Pages: 853-867
DOI
NAID
Related Report
Peer Reviewed
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[Journal Article] Regeneration of tumor antigen-specific CTLs utilizing iPS technology2016
Author(s)
Kataoka K, Shiraishi Y, Takeda Y, Sakata S, Matsumoto M, Suzuki H, Yoshiato T, Yoshida K, Sanada M. Itonaga H, Imaizumi Y, Totoki Y, Munakata W, Nakamura H, Hama N, Shide K, Kubuki Y, Hidaka T, Kameda T, Masuda K, et al.
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Journal Title
Rinsho Ketsueki
Volume: 57
Issue: 8
Pages: 1066-1073
DOI
NAID
ISSN
0485-1439, 1882-0824
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Heterogeneous fibroblasts underlie age-dependent tertiary lymphoid tissues in the kidney2016
Author(s)
Sato Y, Mii A, Hamazaki Y, Fujita H, Nakata H, Masuda K, Nishiyama S, Shibuya S, Haga H, Ogawa O, Shimizu A, Narumiya S, Kaisho T, Arita M, Yanagisawa M, Miyasaka M, Sharma K, Minato N, Kawamoto H, and Yanagita M.
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Journal Title
JCI. Insight.
Volume: 1
Issue: 11
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Regeneration of CD8αβ T cells from T cell-derived iPSC imparts potent tumor antigen-specific cytotoxicity.2016
Author(s)
Maeda T, Nagano S, Ichise H, Kataoka K, Yamada D, Ogawa S, Koseki H, Kitawaki T, Kadowaki N, Takaori-Kondo A, Masuda K, Kawamoto H
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Journal Title
Cancer Research
Volume: 76
Issue: 23
Pages: 6839-6850
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Conversion of T cells to B cells by inactivation of polycomb-mediated epigenetic suppression of the B-lineage program.2016
Author(s)
Ikawa T, Masuda K, Endo TA, Endo M, Isono K, Koseki Y, Nakagawa R, Kometani K, Takano J, Agata Y, Katsura Y, Kurosaki T, Vidal M, Koseki H, Kawamoto H.
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Journal Title
Genes. Dev.
Volume: 30
Issue: 22
Pages: 2475-2485
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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