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Discovery of human B-lymphoid/plasmacytoid dendritic cell bifurcation with largely fluctuating transcriptome dynamics by an advanced lymphoid culture system and a newly developed AI-based methodology

8 Nov 2022

Summary of our research

Research group, including Dr. Keiki Nagaharu (Graduate student, Mie University Graduate School of Medicne), Dr. Kohshi Ohishi (Director & Associate Professor, Transfusion Medicine and Cell Therapy, Mie University Hospital), Dr. Yasuhiro Kojima (Specially Appointed Lecturer, Division of Systems Biology, Nagoya University Graduate School of Medicine), Dr. Teppei Shimamura (Professor, Division of Systems Biology, Nagoya University Graduate School of Medicine), and Dr. Hiroyoshi Nishikawa (Professor, Department of Immunology, Nagoya University Graduate School of Medicine & Division of Cancer Immunology, Research Institute, National Cancer Center), discovered that B cells (which produce antibody) and plasmacytoid denderitic cells (pDCs)(which produce type 1 interferon in response to a viral infection) originate from common progenitors with strong fluctuation of trasncriptome dynamics and that LFA-1 fluctuates positively in the pDC direction at the bifurcation, using an original computational methodology and an advanced lymphoid coculture system. Furthremore, single cell multiome analysis revealed that the differentially accessible chromatin regions of B cells and pDCs were simultaneously accessible in the cell population with a large fluctuation of transcriptome dynamics by suport of "Platform for Advanced Genome Science" (PAGS). Hematopoiesis was considered a hierarchical stepwise process, but revised to a continuous process by single cell RNA-sequencing. We provide a new model of differentiation, fluctuation-based differentiation, which reconciles continuous and discrete models.

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Researcher information

Photo of NAGAHARU Keiki

NAGAHARU Keiki

Graduate student (present Research Associate), Department of Hematology and Oncology, Mie University Graduate School of Medicine (present Yokkaichi Municipal Hospital)

Specialized area:

Hematology

Current research field:

Eluciadation of molecular mechanism and fibrosis of myeloproliferative neaoplasms

Photo of OHISHI Kohshi

OHISHI Kohshi

Director, Associate Professor, Transfusion Medicine and Cell Therapy, Mie University Hospital

Specialized area:

Hematology, trasnfusion, HIV infection

Current research field:

Elucidation of human lymphoid pathway and novel differentiation mechanism