2022 Fiscal Year Final Research Report
Elucidating the roles of cell surface glycans on epithelial stem cell aging
| Project/Area Number |
20K21431
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 44:Biology at cellular to organismal levels, and related fields
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| Research Institution | Kumamoto University |
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Principal Investigator |
Sada Aiko 熊本大学, 国際先端医学研究機構, 特任准教授 (80779059)
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| Co-Investigator(Kenkyū-buntansha) |
舘野 浩章 国立研究開発法人産業技術総合研究所, 生命工学領域, 研究グループ長 (30450670)
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| Project Period (FY) |
2020-07-30 – 2023-03-31
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| Keywords | 糖鎖 / 表皮幹細胞 / 皮膚老化 / レクチン / シアル酸 |
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| Outline of Final Research Achievements |
Glycosylation of membrane proteins has been suggested to regulate stem cell-niche interactions and cell behavior in response to various environmental stimuli. We have previously shown that epidermal stem cells from young and old mice exhibited distinct glycan profiles, with an upregulation of glycogenes such as St6gal1, St3gal2, and Man1a. However, the functional role of these glycan changes in skin aging remains unknown. In this study, we found that overexpression of St6gal1, St3gal2, and Man1a altered the glycan profile of epidermal stem cell membrane proteins in vivo. Mice overexpressing St6gal1 and Man1a exhibited phenotypes associated with skin aging, including the impaired epidermal structure and decreased proliferation. Mass spectrometry using membrane proteins pulled down by lectins showed the binding of several core protein candidates. Thus, this study showed the functional importance of glycogenes in vivo, which provide a glycan-based strategy for controlling skin aging.
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| Free Research Field |
皮膚科学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、糖鎖構造を高感度かつ迅速に検出することが可能なレクチン技術を用い、皮膚幹細胞の糖鎖修飾パターンの加齢変化を捉え、その機能の一端を解明することに成功した。糖鎖は、DNA、タンパク質に次ぐ「第3の生命鎖」と呼ばれ、近年注目を集めているが、少量の生体サンプルを用いた解析が困難であり理解が遅れていた。本成果は、糖鎖解析の最先端技術の開発に取り組む研究グループと協働することで生み出された成果であり、幹細胞の糖鎖を標的とした新たな老化制御や老化状態を早い段階で予測するバイオマーカーの創出へとつながることが期待される。
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