Glycomic study of podocalyxin from human induced pluripotent stem cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07003
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47020:Pharmaceutical analytical chemistry and physicochemistry-related
• Research Institution: Ritsumeikan University
• Principal Investigator: Toyoda Hidenao 立命館大学, 薬学部, 教授 (70217579)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: グリコサミノグリカン / iPS細胞 / ポドカリキシン / ケラタン硫酸

Outline of Final Research Achievements

Podocalyxin (PC) was initially identified as a sialylated glycoconjugate in rat glomerular podocytes. Recently, many epitopes of undifferentiated state markers in human iPS cells have been found to be glycans attached to PC. Thus, the elucidation of glycan structures in PC from human iPS cells is required for the progress of regenerative medicine. PC is a protein with a calculated molecular weight of 55 kDa, although various molecular weights have been reported, presumably due to post-translational glycosylation. In this study, the molecular weight of PC in human iPS cells has been shown to be >720 kDa by blue native PAGE. Then, we have devised methods for the analysis of sialic acids and keratan sulfates. It was clarified that PC in human iPS cells is heavily sialylated. Furthermore, very low-sulfated keratan sulfates with poly N-acetyl lactosamine structures were found, and this unique structure seems to have a significant role in the undifferentiated state of human iPS cells.

Free Research Field

糖鎖生物学

Academic Significance and Societal Importance of the Research Achievements

ヒトiPS細胞の研究で使用されている未分化マーカーの多くは、ポドカリキシン上のケラタン硫酸様糖鎖を認識していると推測されている。しかしながらヒトiPS細胞を用いた分析化学的な糖鎖研究例は少なく、特にケラタン硫酸の分析は非常に高度な技術を要するため、その詳細は国内外で大きな注目を集めている。ポドカリキシンはがん細胞の悪性度マーカーという側面もあるために，幹細胞研究のみならず、がん研究の面からもポドカリキシンの糖鎖研究は大きな意義を持っている。以上のことから、本研究で明らかにされた、ヒトiPS細が産生しているポドカリキシン上の糖鎖構造の情報は、様々な研究分野の進展に大きく寄与するものと考えられる。