Frontiers in Cell and Developmental Biology (Jul 2021)
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
- Heng-Kien Au,
- Heng-Kien Au,
- Heng-Kien Au,
- Heng-Kien Au,
- Heng-Kien Au,
- Syue-Wei Peng,
- Syue-Wei Peng,
- Chin-Lin Guo,
- Chien-Chia Lin,
- Chien-Chia Lin,
- Yi-Lin Wang,
- Yi-Lin Wang,
- Yung-Che Kuo,
- Yung-Che Kuo,
- Tsz-Yau Law,
- Tsz-Yau Law,
- Hong-Nerng Ho,
- Hong-Nerng Ho,
- Hong-Nerng Ho,
- Thai-Yen Ling,
- Yen-Hua Huang,
- Yen-Hua Huang,
- Yen-Hua Huang,
- Yen-Hua Huang,
- Yen-Hua Huang,
- Yen-Hua Huang,
- Yen-Hua Huang
Affiliations
- Heng-Kien Au
- Taipei Medical University (TMU) Research Center of Cell Therapy and Regeneration Medicine, Taipei Medical University, Taipei, Taiwan
- Heng-Kien Au
- Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Heng-Kien Au
- Department of Obstetrics and Gynecology, Taipei Medical University Hospital, Taipei, Taiwan
- Heng-Kien Au
- Center for Reproductive Medicine, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan
- Heng-Kien Au
- International Ph.D. Program for Cell Therapy and Regeneration Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Syue-Wei Peng
- Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Syue-Wei Peng
- Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Chin-Lin Guo
- Institute of Physics, Academia Sinica, Taipei, Taiwan
- Chien-Chia Lin
- Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Chien-Chia Lin
- Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Yi-Lin Wang
- Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Yi-Lin Wang
- Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Yung-Che Kuo
- Taipei Medical University (TMU) Research Center of Cell Therapy and Regeneration Medicine, Taipei Medical University, Taipei, Taiwan
- Yung-Che Kuo
- Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Tsz-Yau Law
- Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Tsz-Yau Law
- Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Hong-Nerng Ho
- Taipei Medical University (TMU) Research Center of Cell Therapy and Regeneration Medicine, Taipei Medical University, Taipei, Taiwan
- Hong-Nerng Ho
- Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Hong-Nerng Ho
- Department of Obstetrics and Gynecology, Taipei Municipal Wanfang Hospital, Taipei, Taiwan
- Thai-Yen Ling
- 0Department and Graduate Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan
- Yen-Hua Huang
- Taipei Medical University (TMU) Research Center of Cell Therapy and Regeneration Medicine, Taipei Medical University, Taipei, Taiwan
- Yen-Hua Huang
- Center for Reproductive Medicine, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan
- Yen-Hua Huang
- International Ph.D. Program for Cell Therapy and Regeneration Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Yen-Hua Huang
- Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Yen-Hua Huang
- Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Yen-Hua Huang
- 1Comprehensive Cancer Center of Taipei Medical University, Taipei, Taiwan
- Yen-Hua Huang
- 2The Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan
- DOI
- https://doi.org/10.3389/fcell.2021.646644
- Journal volume & issue
-
Vol. 9
Abstract
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.
Keywords
