Elucidation of molecular mechanism of the robustness between T and B cell lineage

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09870
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Kyoto University
• Principal Investigator: Masuda Kyoko 京都大学, ウイルス・再生医科学研究所, 助教 (40565777)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 系列決定 / 系列頑健性 / ポリコーム遺伝子

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.

Free Research Field

免疫学

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。