https://scholars.lib.ntu.edu.tw/handle/123456789/583820
標題: | Niche Laminin and IGF-1 Additively Coordinate the Maintenance of Oct-4 Through CD49f/IGF-1R-Hif-2α Feedforward Loop in Mouse Germline Stem Cells | 作者: | Au, Heng-Kien Peng, Syue-Wei Guo, Chin-Lin Lin, Chien-Chia Wang, Yi-Lin Kuo, Yung-Che Law, Tsz-Yau HONG-NERNG HO THAI-YEN LING Huang, Yen-Hua |
關鍵字: | IGF; extracellular matrix; germline stem cell; hypoxia; laminin; niche; self-renewal | 公開日期: | 2021 | 卷: | 9 | 來源出版物: | Frontiers in cell and developmental biology | 摘要: | The mechanism on how extracellular matrix (ECM) cooperates with niche growth factors and oxygen tension to regulate the self-renewal of embryonic germline stem cells (GSCs) still remains unclear. Lacking of an appropriate in vitro cell model dramatically hinders the progress. Herein, using a serum-free culture system, we demonstrated that ECM laminin cooperated with hypoxia and insulin-like growth factor 1 receptor (IGF-1R) to additively maintain AP activity and Oct-4 expression of AP+GSCs. We found the laminin receptor CD49f expression in d2 testicular GSCs that were surrounded by laminin. Laminin and hypoxia significantly increased the GSC stemness-related genes, including Hif-2α, Oct-4, IGF-1R, and CD49f. Cotreatment of IGF-1 and laminin additively increased the expression of IGF-IR, CD49f, Hif-2α, and Oct-4. Conversely, silencing IGF-1R and/or CD49f decreased the expression of Hif-2α and Oct-4. The underlying mechanism involved CD49f/IGF1R-(PI3K/AKT)-Hif-2α signaling loop, which in turn maintains Oct-4 expression, symmetric self-renewal, and cell migration. These findings reveal the additive niche laminin/IGF-IR network during early GSC development. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/583820 | ISSN: | 2296-634X | DOI: | 10.3389/fcell.2021.646644 |
顯示於: | 醫學系 |
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