Role of Polycomb proteins in lymphocyte cell fate decision

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H04214
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Tokyo University of Science
• Principal Investigator: Ikawa Tomokatsu 東京理科大学, 研究推進機構生命医科学研究所, 教授 (60450392)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: エピジェネティクス / 造血幹細胞 / B細胞分化 / 運命決定 / 転写因子

Outline of Final Research Achievements

T cells and B cells are generated from hematopoietic stem cells (HSCs). HSCs gradually specify their fates to finally commit to the B cell lineage. Transcription factors and epigenetic modification play pivotal roles in the cell fate decision. However, the molecular mechanisms are largely unknown. We have recently found that the Polycomb group protein, PCGF1 was important for the B cell lineage specification from HSCs. B cell development in bone marrow of PCGF1-deficient mice was severely impaired, while T cells were normally generated. The expression of meyloid and stem cell genes was derepressed in PCGF1-deficent hematopoietic progenitors. Knock-down of the upregulated genes partially restored the B cell generation. Thus, these results indicate that PCGF1 is an essential epigenetic regulator for early B cell differentiation.

Free Research Field

免疫学、血液学

Academic Significance and Societal Importance of the Research Achievements

抗体産生を担うB細胞は骨髄中で造血幹細胞から作られるが、そのメカニズムは未だ不明な点が多い。特に、造血幹細胞からどのようにB細胞系列へ運命決定されるのか明らかでない。本研究により、B細胞の生成に重要な分子機構の一端が明らかとなった。この知見は白血病を含む造血器腫瘍の発症機構の解明に寄与すると考えられる。また、分化の分子機構が明らかになれば、免疫細胞療法や再生医療への応用が期待される。