Biological role and differentiation mechanism of lymphoid-origin dendritic cells and B1B cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08389
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Mie University
• Principal Investigator: Ohishi Kohshi 三重大学, 医学部附属病院, 准教授 (00397506)
• Co-Investigator(Kenkyū-buntansha): 永春 圭規 三重大学, 医学系研究科, リサーチアソシエイト (80883462)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: lymphoid differentaition / B / plasmacytoid DC / scRNAseq / LFA-1 / fluctutation / differentiation model / human

Outline of Final Research Achievements

Using a method that combines comprehensive lymphocyte culture and the integration of deep generative models with splicing mathematical models, we have quantitatively analyzed the "fluctuations" in the directionality of cell differentiation at the single-cell level of RNA gene expression through scRNA-seq. We have discovered that human B lymphocytes involved in antibody production and plasmacytoid dendritic cells share a common progenitor cell origin. At this branching point, there is significant fluctuation in directionality. We have also identified the involvement of the adhesion molecule LFA-1 in the fluctuation towards pDC differentiation. Furthermore, using ATAC-seq, we have revealed that the accessibility of transcription factors associated with B and pDC differentiation is high in both cell types.

Free Research Field

血液学

Academic Significance and Societal Importance of the Research Achievements

造血幹細胞は、骨髄球系とリンパ球系に分化し、さらに段階的・断続的に分化・分岐していくと考えられていたが、リンパ球系分化から樹状細胞や単球が分化することから見直しが必要とされている。研究代表者らは、独自の培養法とscRNAseq解析法により、ヒトBリンパ球系細胞と形質細胞様樹状細胞の共通の前駆細胞を同定するとともに、scRNAseq解析では細胞分化は連続的(continuous)に起きると考えられていたが、この細胞分岐では分化方向性が大きくゆれることを明らかにし、揺らぎに基づく新しい分化モデル(fluctuation-based differentiation model)を提唱した。