Determining differentiation from ES cells by localization of signal receptors on the cell membrane

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06139
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43030:Functional biochemistry-related
• Research Institution: Soka University
• Principal Investigator: Nishihara Shoko 創価大学, 糖鎖生命システム融合研究所, 教授 (00164575)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 糖鎖 / マウスES細胞 / シグナル

Outline of Final Research Achievements

Mouse ES cells are pluripotent stem cells; they differentiate into epiblast or primitive endoderm when the differentiation is triggered. On the other hand, studies including us have revealed that signal receptors are selectively localized in lipid rafts on the cell membrane, and that localization is essential for signal transduction.
In this study, we focused on the glycolipids that constitute lipid rafts in mouse ES cells and analyzed changes in their composition during differentiation of mouse ES cells into epiblast stem cells. Then, we found a novel mechanism that totally controls the glycosyltransferases responsible for these changes. These results suggest that glycolipid changes may be involved in the exit from undifferentiation state and the decision to differentiate.

Free Research Field

糖鎖生物学、幹細胞生物学

Academic Significance and Societal Importance of the Research Achievements

本研究の遂行の過程で、マウスES細胞の分化における、糖脂質をはじめとする細胞表面の糖鎖構造をトータルに制御する機構が初めて明らかになり、糖脂質を含む糖鎖の変化がES細胞からの分化に統一して関与している可能性が見出された。糖脂質や糖タンパク質上の糖鎖構造が一緒に制御を受けていることを示した例は、これまでになく、学術的な意義も大きい。また、様々な分化細胞をES細胞から作製する再生医療への応用の基盤形成にも寄与する。