Dissection of immune cell differentiation by a single cel epigenome analysis

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K19569
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 54:Internal medicine of the bio-information integration and related fields
• 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): 2018-06-29 – 2020-03-31
• Keywords: B細胞分化 / 造血幹細胞 / 転写因子 / エピジェネティクス / 運命決定

Outline of Final Research Achievements

Immune cells including 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 cooperate in the cell fate decision. However, the molecular mechanisms are yet to be determined. We have recently established the multipotent progenitor cell line named iLS (induced Leukocyte Stem) cells. iLS cells maintain the differentiation potential for T, B and myeloid lineage cells with unlimited self-renewal capacity. We have explored the single cell transcriptome profile of B lineage commitment using the iLS cells differentiating into B cells. Synchronous and cascading expression of key transcription factors and epigenetic factors was disclosed based on the single cell RNA-seq analysis. Thus the data provide a blueprint for studying the normal and malignant B cell generation.

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遺伝子制御機構が1細胞レベルで明らかとなった。この知見は正常な免疫細胞分化のメカニズムだけでなく、白血病を含む様々な造血器腫瘍の発症機構の解明に貢献すると考えられる。今後、分化の分子機構がさらに明らかになれば、免疫細胞療法や再生医療への応用が期待される。