Controlling pluripotent stem cells by sugar chains - Can maintenance and differentiation of pluripotency be obtained by modifying biosynthetic pathway of sugar chain?

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K07786
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Integrative animal science
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: AIKAWA JUNICHI 国立研究開発法人理化学研究所, 開拓研究本部, 専任研究員 (10260192)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 多能性幹細胞 / ES細胞 / 糖鎖 / ゴルジマンノシダーゼ / レチノイン酸

Outline of Final Research Achievements

This study aimed to clarify the relationship between the properties of pluripotent stem cells and the biosynthesis of asparagine-linked sugar chains. First, the mannosidase inhibitor, which also inhibit the activity of mouse mannosidase IA (mMAN1A1) localized to the Golgi apparatus, was added in a system where mouse embryonic stem cells were differentiated by the addition of retinoic acid. Although the sugar chain structure was significantly changed, no significant change was observed in the cell morphology which is an indicator of differentiation. Next, the expression pattern of transcripts found in the region upstream of the transcription start point of mMAN1A1 was analyzed by RT-PCR. As a result, it was found that the expression of a partial region of the predicted transcript changes with differentiation of mouse embryonic stem cells.

Free Research Field

糖鎖工学

Academic Significance and Societal Importance of the Research Achievements

本研究課題は多能性幹細胞の性状とアスパラギン結合型糖鎖の生合成の関係を明らかにすることを目的とした。マウスのゴルジ体に局在するマンノシダーゼIA(mMAN1A1)に見い出された転写産物の発現を制御することで、アスパラギン結合型糖鎖のパターンが変化する可能性が示された。分化や疾病との関係解明が期待される。mMAN1A1の活性を抑制する阻害剤ではマウス胚性幹細胞では形態レベルでは顕著な変化が見られなかったが、他の分化系での試験が引き続き必要である。