LIF Promotes Sec15b‐Mediated STAT3 Exosome Secretion to Maintain Stem Cell Pluripotency in Mouse Embryonic Development
Abstract LIF maintains self‐renewal growth in mouse embryonic stem cells (mESC) by activating STAT3, which translocates into nucleus for pluripotent gene induction. However, the ERK signaling pathway activated by LIF at large counteract with pluripotent gene induction during self‐renewal growth. Her...
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Wiley
2024-12-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202407971 |
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| author | Li Xu Jinjun Ji Lingbo Wang Jieli Pan Mingzhe Xiao Chenxi Zhang Yihong Gan Guanqun Xie Mingdian Tan Xinchang Wang Chengping Wen Yongsheng Fan Y. Eugene Chin |
| author_facet | Li Xu Jinjun Ji Lingbo Wang Jieli Pan Mingzhe Xiao Chenxi Zhang Yihong Gan Guanqun Xie Mingdian Tan Xinchang Wang Chengping Wen Yongsheng Fan Y. Eugene Chin |
| author_sort | Li Xu |
| collection | DOAJ |
| description | Abstract LIF maintains self‐renewal growth in mouse embryonic stem cells (mESC) by activating STAT3, which translocates into nucleus for pluripotent gene induction. However, the ERK signaling pathway activated by LIF at large counteract with pluripotent gene induction during self‐renewal growth. Here, it is reported that in mESC STAT3 undergoes multivesicular endosomes (MVEs) translocation and subsequent secretion, LIF‐activated STAT3 is acetylated on K177/180 and phosphorylated on Y293 residues within the N‐terminal coiled‐coil domain, which is responsible for the interaction between STAT3 and Secl5b, an exocyst complex component 6B (EXOC6B). STAT3 translocation into MVEs resulted in the downregulation of T202/Y204‐ERK1/2 phosphorylation and up‐regulation of S9‐GSK3β phosphorylation for maintaining mESC self‐renewal growth. STAT3 with K177R/K180R or Y293F substitution fails to execute MVEs translocation and Secl5b‐dependent secretion. Mice expressing K177RK180R substitution (STAT3mut/mut) are partially embryonic lethal. In STAT3mut/mut embryos, gene expressions related to hematological system function changed significantly and those living ones carry a series of abnormalities in the hematopoietic system. Furthermore, mice with Secl5b knockout exhibit embryonic lethality. Thus, Secl5b mediated STAT3 MVEs translocation regulates the balance of ERK and GSK3β signaling pathways and maintain mESC self‐renewal growth, which is involved in regulating the stability of hematopoietic system. |
| format | Article |
| id | doaj-art-185fb90f4f574119a79f539eddec2442 |
| institution | DOAJ |
| issn | 2198-3844 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wiley |
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| series | Advanced Science |
| spelling | doaj-art-185fb90f4f574119a79f539eddec24422025-08-20T02:55:53ZengWileyAdvanced Science2198-38442024-12-011148n/an/a10.1002/advs.202407971LIF Promotes Sec15b‐Mediated STAT3 Exosome Secretion to Maintain Stem Cell Pluripotency in Mouse Embryonic DevelopmentLi Xu0Jinjun Ji1Lingbo Wang2Jieli Pan3Mingzhe Xiao4Chenxi Zhang5Yihong Gan6Guanqun Xie7Mingdian Tan8Xinchang Wang9Chengping Wen10Yongsheng Fan11Y. Eugene Chin12College of Basic Medical Science Zhejiang Chinese Medical University 548 Binwen Road Hangzhou 310051 ChinaCollege of Basic Medical Science Zhejiang Chinese Medical University 548 Binwen Road Hangzhou 310051 ChinaClinical Medicine Research Institute Zhejiang Provincial People's Hospital Hangzhou Medical College 158 Shangtang Road Hangzhou Zhejiang 310014 ChinaCollege of Basic Medical Science Zhejiang Chinese Medical University 548 Binwen Road Hangzhou 310051 ChinaClinical Medicine Research Institute Zhejiang Provincial People's Hospital Hangzhou Medical College 158 Shangtang Road Hangzhou Zhejiang 310014 ChinaClinical Medicine Research Institute Zhejiang Provincial People's Hospital Hangzhou Medical College 158 Shangtang Road Hangzhou Zhejiang 310014 ChinaCollege of Basic Medical Science Zhejiang Chinese Medical University 548 Binwen Road Hangzhou 310051 ChinaCollege of Basic Medical Science Zhejiang Chinese Medical University 548 Binwen Road Hangzhou 310051 ChinaClinical Medicine Research Institute Zhejiang Provincial People's Hospital Hangzhou Medical College 158 Shangtang Road Hangzhou Zhejiang 310014 ChinaDepartment of Rheumatology The Second Affiliated Hospital of Zhejiang Chinese Medical University Hangzhou 310005 ChinaCollege of Basic Medical Science Zhejiang Chinese Medical University 548 Binwen Road Hangzhou 310051 ChinaCollege of Basic Medical Science Zhejiang Chinese Medical University 548 Binwen Road Hangzhou 310051 ChinaClinical Medicine Research Institute Zhejiang Provincial People's Hospital Hangzhou Medical College 158 Shangtang Road Hangzhou Zhejiang 310014 ChinaAbstract LIF maintains self‐renewal growth in mouse embryonic stem cells (mESC) by activating STAT3, which translocates into nucleus for pluripotent gene induction. However, the ERK signaling pathway activated by LIF at large counteract with pluripotent gene induction during self‐renewal growth. Here, it is reported that in mESC STAT3 undergoes multivesicular endosomes (MVEs) translocation and subsequent secretion, LIF‐activated STAT3 is acetylated on K177/180 and phosphorylated on Y293 residues within the N‐terminal coiled‐coil domain, which is responsible for the interaction between STAT3 and Secl5b, an exocyst complex component 6B (EXOC6B). STAT3 translocation into MVEs resulted in the downregulation of T202/Y204‐ERK1/2 phosphorylation and up‐regulation of S9‐GSK3β phosphorylation for maintaining mESC self‐renewal growth. STAT3 with K177R/K180R or Y293F substitution fails to execute MVEs translocation and Secl5b‐dependent secretion. Mice expressing K177RK180R substitution (STAT3mut/mut) are partially embryonic lethal. In STAT3mut/mut embryos, gene expressions related to hematological system function changed significantly and those living ones carry a series of abnormalities in the hematopoietic system. Furthermore, mice with Secl5b knockout exhibit embryonic lethality. Thus, Secl5b mediated STAT3 MVEs translocation regulates the balance of ERK and GSK3β signaling pathways and maintain mESC self‐renewal growth, which is involved in regulating the stability of hematopoietic system.https://doi.org/10.1002/advs.202407971cell pluripotencyexosomemultivesicular endosomes (MVEs)STAT3Sec15b |
| spellingShingle | Li Xu Jinjun Ji Lingbo Wang Jieli Pan Mingzhe Xiao Chenxi Zhang Yihong Gan Guanqun Xie Mingdian Tan Xinchang Wang Chengping Wen Yongsheng Fan Y. Eugene Chin LIF Promotes Sec15b‐Mediated STAT3 Exosome Secretion to Maintain Stem Cell Pluripotency in Mouse Embryonic Development Advanced Science cell pluripotency exosome multivesicular endosomes (MVEs) STAT3 Sec15b |
| title | LIF Promotes Sec15b‐Mediated STAT3 Exosome Secretion to Maintain Stem Cell Pluripotency in Mouse Embryonic Development |
| title_full | LIF Promotes Sec15b‐Mediated STAT3 Exosome Secretion to Maintain Stem Cell Pluripotency in Mouse Embryonic Development |
| title_fullStr | LIF Promotes Sec15b‐Mediated STAT3 Exosome Secretion to Maintain Stem Cell Pluripotency in Mouse Embryonic Development |
| title_full_unstemmed | LIF Promotes Sec15b‐Mediated STAT3 Exosome Secretion to Maintain Stem Cell Pluripotency in Mouse Embryonic Development |
| title_short | LIF Promotes Sec15b‐Mediated STAT3 Exosome Secretion to Maintain Stem Cell Pluripotency in Mouse Embryonic Development |
| title_sort | lif promotes sec15b mediated stat3 exosome secretion to maintain stem cell pluripotency in mouse embryonic development |
| topic | cell pluripotency exosome multivesicular endosomes (MVEs) STAT3 Sec15b |
| url | https://doi.org/10.1002/advs.202407971 |
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