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
Copyright © 2021 Au, Peng, Guo, Lin, Wang, Kuo, Law, Ho, Ling and Huang..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:9 |
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| Enthalten in: |
Frontiers in cell and developmental biology - 9(2021) vom: 27., Seite 646644 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Au, Heng-Kien [VerfasserIn] |
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| Links: |
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| Themen: |
Extracellular matrix |
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| Anmerkungen: |
Date Revised 13.08.2021 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.3389/fcell.2021.646644 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM329256572 |
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| 520 | |a Copyright © 2021 Au, Peng, Guo, Lin, Wang, Kuo, Law, Ho, Ling and Huang. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a IGF | |
| 650 | 4 | |a extracellular matrix | |
| 650 | 4 | |a germline stem cell | |
| 650 | 4 | |a hypoxia | |
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| 650 | 4 | |a niche | |
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| 700 | 1 | |a Peng, Syue-Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Chin-Lin |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Chien-Chia |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yi-Lin |e verfasserin |4 aut | |
| 700 | 1 | |a Kuo, Yung-Che |e verfasserin |4 aut | |
| 700 | 1 | |a Law, Tsz-Yau |e verfasserin |4 aut | |
| 700 | 1 | |a Ho, Hong-Nerng |e verfasserin |4 aut | |
| 700 | 1 | |a Ling, Thai-Yen |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Yen-Hua |e verfasserin |4 aut | |
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