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
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-f...
Ausführliche Beschreibung
Autor*in: |
Heng-Kien Au [verfasserIn] Syue-Wei Peng [verfasserIn] Chin-Lin Guo [verfasserIn] Chien-Chia Lin [verfasserIn] Yi-Lin Wang [verfasserIn] Yung-Che Kuo [verfasserIn] Tsz-Yau Law [verfasserIn] Hong-Nerng Ho [verfasserIn] Thai-Yen Ling [verfasserIn] Yen-Hua Huang [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2021 |
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Schlagwörter: |
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Übergeordnetes Werk: |
In: Frontiers in Cell and Developmental Biology - Frontiers Media S.A., 2014, 9(2021) |
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Übergeordnetes Werk: |
volume:9 ; year:2021 |
Links: |
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DOI / URN: |
10.3389/fcell.2021.646644 |
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Katalog-ID: |
DOAJ058529004 |
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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. | ||
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10.3389/fcell.2021.646644 doi (DE-627)DOAJ058529004 (DE-599)DOAJb689affe981b4728ba7db464478e1c2e DE-627 ger DE-627 rakwb eng QH301-705.5 Heng-Kien Au verfasserin aut 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 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. germline stem cell niche extracellular matrix hypoxia laminin IGF Biology (General) Heng-Kien Au verfasserin aut Heng-Kien Au verfasserin aut Heng-Kien Au verfasserin aut Heng-Kien Au verfasserin aut Syue-Wei Peng verfasserin aut Syue-Wei Peng verfasserin aut Chin-Lin Guo verfasserin aut Chien-Chia Lin verfasserin aut Chien-Chia Lin verfasserin aut Yi-Lin Wang verfasserin aut Yi-Lin Wang verfasserin aut Yung-Che Kuo verfasserin aut Yung-Che Kuo verfasserin aut Tsz-Yau Law verfasserin aut Tsz-Yau Law verfasserin aut Hong-Nerng Ho verfasserin aut Hong-Nerng Ho verfasserin aut Hong-Nerng Ho verfasserin aut Thai-Yen Ling verfasserin aut Yen-Hua Huang verfasserin aut Yen-Hua Huang verfasserin aut Yen-Hua Huang verfasserin aut Yen-Hua Huang verfasserin aut Yen-Hua Huang verfasserin aut Yen-Hua Huang verfasserin aut Yen-Hua Huang verfasserin aut In Frontiers in Cell and Developmental Biology Frontiers Media S.A., 2014 9(2021) (DE-627)770398138 (DE-600)2737824-X 2296634X nnns volume:9 year:2021 https://doi.org/10.3389/fcell.2021.646644 kostenfrei https://doaj.org/article/b689affe981b4728ba7db464478e1c2e kostenfrei https://www.frontiersin.org/articles/10.3389/fcell.2021.646644/full kostenfrei https://doaj.org/toc/2296-634X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2021 |
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10.3389/fcell.2021.646644 doi (DE-627)DOAJ058529004 (DE-599)DOAJb689affe981b4728ba7db464478e1c2e DE-627 ger DE-627 rakwb eng QH301-705.5 Heng-Kien Au verfasserin aut 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 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. germline stem cell niche extracellular matrix hypoxia laminin IGF Biology (General) Heng-Kien Au verfasserin aut Heng-Kien Au verfasserin aut Heng-Kien Au verfasserin aut Heng-Kien Au verfasserin aut Syue-Wei Peng verfasserin aut Syue-Wei Peng verfasserin aut Chin-Lin Guo verfasserin aut Chien-Chia Lin verfasserin aut Chien-Chia Lin verfasserin aut Yi-Lin Wang verfasserin aut Yi-Lin Wang verfasserin aut Yung-Che Kuo verfasserin aut Yung-Che Kuo verfasserin aut Tsz-Yau Law verfasserin aut Tsz-Yau Law verfasserin aut Hong-Nerng Ho verfasserin aut Hong-Nerng Ho verfasserin aut Hong-Nerng Ho verfasserin aut Thai-Yen Ling verfasserin aut Yen-Hua Huang verfasserin aut Yen-Hua Huang verfasserin aut Yen-Hua Huang verfasserin aut Yen-Hua Huang verfasserin aut Yen-Hua Huang verfasserin aut Yen-Hua Huang verfasserin aut Yen-Hua Huang verfasserin aut In Frontiers in Cell and Developmental Biology Frontiers Media S.A., 2014 9(2021) (DE-627)770398138 (DE-600)2737824-X 2296634X nnns volume:9 year:2021 https://doi.org/10.3389/fcell.2021.646644 kostenfrei https://doaj.org/article/b689affe981b4728ba7db464478e1c2e kostenfrei https://www.frontiersin.org/articles/10.3389/fcell.2021.646644/full kostenfrei https://doaj.org/toc/2296-634X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2021 |
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10.3389/fcell.2021.646644 doi (DE-627)DOAJ058529004 (DE-599)DOAJb689affe981b4728ba7db464478e1c2e DE-627 ger DE-627 rakwb eng QH301-705.5 Heng-Kien Au verfasserin aut 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 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. germline stem cell niche extracellular matrix hypoxia laminin IGF Biology (General) Heng-Kien Au verfasserin aut Heng-Kien Au verfasserin aut Heng-Kien Au verfasserin aut Heng-Kien Au verfasserin aut Syue-Wei Peng verfasserin aut Syue-Wei Peng verfasserin aut Chin-Lin Guo verfasserin aut Chien-Chia Lin verfasserin aut Chien-Chia Lin verfasserin aut Yi-Lin Wang verfasserin aut Yi-Lin Wang verfasserin aut Yung-Che Kuo verfasserin aut Yung-Che Kuo verfasserin aut Tsz-Yau Law verfasserin aut Tsz-Yau Law verfasserin aut Hong-Nerng Ho verfasserin aut Hong-Nerng Ho verfasserin aut Hong-Nerng Ho verfasserin aut Thai-Yen Ling verfasserin aut Yen-Hua Huang verfasserin aut Yen-Hua Huang verfasserin aut Yen-Hua Huang verfasserin aut Yen-Hua Huang verfasserin aut Yen-Hua Huang verfasserin aut Yen-Hua Huang verfasserin aut Yen-Hua Huang verfasserin aut In Frontiers in Cell and Developmental Biology Frontiers Media S.A., 2014 9(2021) (DE-627)770398138 (DE-600)2737824-X 2296634X nnns volume:9 year:2021 https://doi.org/10.3389/fcell.2021.646644 kostenfrei https://doaj.org/article/b689affe981b4728ba7db464478e1c2e kostenfrei https://www.frontiersin.org/articles/10.3389/fcell.2021.646644/full kostenfrei https://doaj.org/toc/2296-634X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2021 |
allfieldsGer |
10.3389/fcell.2021.646644 doi (DE-627)DOAJ058529004 (DE-599)DOAJb689affe981b4728ba7db464478e1c2e DE-627 ger DE-627 rakwb eng QH301-705.5 Heng-Kien Au verfasserin aut 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 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. germline stem cell niche extracellular matrix hypoxia laminin IGF Biology (General) Heng-Kien Au verfasserin aut Heng-Kien Au verfasserin aut Heng-Kien Au verfasserin aut Heng-Kien Au verfasserin aut Syue-Wei Peng verfasserin aut Syue-Wei Peng verfasserin aut Chin-Lin Guo verfasserin aut Chien-Chia Lin verfasserin aut Chien-Chia Lin verfasserin aut Yi-Lin Wang verfasserin aut Yi-Lin Wang verfasserin aut Yung-Che Kuo verfasserin aut Yung-Che Kuo verfasserin aut Tsz-Yau Law verfasserin aut Tsz-Yau Law verfasserin aut Hong-Nerng Ho verfasserin aut Hong-Nerng Ho verfasserin aut Hong-Nerng Ho verfasserin aut Thai-Yen Ling verfasserin aut Yen-Hua Huang verfasserin aut Yen-Hua Huang verfasserin aut Yen-Hua Huang verfasserin aut Yen-Hua Huang verfasserin aut Yen-Hua Huang verfasserin aut Yen-Hua Huang verfasserin aut Yen-Hua Huang verfasserin aut In Frontiers in Cell and Developmental Biology Frontiers Media S.A., 2014 9(2021) (DE-627)770398138 (DE-600)2737824-X 2296634X nnns volume:9 year:2021 https://doi.org/10.3389/fcell.2021.646644 kostenfrei https://doaj.org/article/b689affe981b4728ba7db464478e1c2e kostenfrei https://www.frontiersin.org/articles/10.3389/fcell.2021.646644/full kostenfrei https://doaj.org/toc/2296-634X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2021 |
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QH301-705.5 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 germline stem cell niche extracellular matrix hypoxia laminin IGF |
topic |
misc QH301-705.5 misc germline stem cell misc niche misc extracellular matrix misc hypoxia misc laminin misc IGF misc Biology (General) |
topic_unstemmed |
misc QH301-705.5 misc germline stem cell misc niche misc extracellular matrix misc hypoxia misc laminin misc IGF misc Biology (General) |
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misc QH301-705.5 misc germline stem cell misc niche misc extracellular matrix misc hypoxia misc laminin misc IGF misc Biology (General) |
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title |
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 |
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title_full |
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 |
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Heng-Kien Au |
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Frontiers in Cell and Developmental Biology |
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Heng-Kien Au Syue-Wei Peng Chin-Lin Guo Chien-Chia Lin Yi-Lin Wang Yung-Che Kuo Tsz-Yau Law Hong-Nerng Ho Thai-Yen Ling Yen-Hua Huang |
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10.3389/fcell.2021.646644 |
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verfasserin |
title_sort |
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 |
callnumber |
QH301-705.5 |
title_auth |
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 |
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. |
abstractGer |
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. |
abstract_unstemmed |
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. |
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title_short |
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 |
url |
https://doi.org/10.3389/fcell.2021.646644 https://doaj.org/article/b689affe981b4728ba7db464478e1c2e https://www.frontiersin.org/articles/10.3389/fcell.2021.646644/full https://doaj.org/toc/2296-634X |
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up_date |
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