LIF Promotes Sec15b-Mediated STAT3 Exosome Secretion to Maintain Stem Cell Pluripotency in Mouse Embryonic Development

被引：0

作者：

Xu, Li ^{[1
]}

Ji, Jinjun ^{[1
]}

Wang, Lingbo ^{[2
,3
]}

Pan, Jieli ^{[1
]}

Xiao, Mingzhe ^{[2
,4
]}

Zhang, Chenxi ^{[2
,4
]}

Gan, Yihong ^{[1
]}

Xie, Guanqun ^{[1
]}

Tan, Mingdian ^{[2
,4
]}

Wang, Xinchang ^{[5
]}

Wen, Chengping ^{[1
]}

Fan, Yongsheng ^{[1
,5
]}

Chin, Y. Eugene ^{[2
,4
]}

机构：

[1] Zhejiang Chinese Med Univ, Coll Basic Med Sci, 548 Binwen Rd, Hangzhou 310051, Peoples R China

[2] Hangzhou Med Coll, Zhejiang Prov Peoples Hosp, Clin Med Res Inst, 158 Shangtang Rd, Hangzhou 310014, Zhejiang, Peoples R China

[3] Chinese Acad Sci, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, Grp Epigenet Reprogramming,State Key Lab Cell Biol, Shanghai 200031, Peoples R China

[4] Chinese Acad Sci, Inst Hlth Sci, Key Lab Stem Cell Biol, Shanghai 200031, Peoples R China

[5] Zhejiang Chinese Med Univ, Affiliated Hosp 2, Dept Rheumatol, Hangzhou 310005, Peoples R China

来源：

ADVANCED SCIENCE | 2024年 / 11卷 / 48期

关键词：

cell pluripotency; exosome; multivesicular endosomes (MVEs); STAT3; Sec15b; SIGNALING PATHWAYS; SELF-RENEWAL; ACTIVATION; EXOCYST; PHOSPHORYLATION; DIFFERENTIATION; ACETYLATION; ASSOCIATION; INHIBITION; TRANSPORT;

D O I：

10.1002/advs.202407971

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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-GSK3 beta 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 GSK3 beta signaling pathways and maintain mESC self-renewal growth, which is involved in regulating the stability of hematopoietic system.

引用

页数：18