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Title 

PRMT8 controls the pluripotency and mesodermal fate of human embryonic stem cells by enhancing the PI3K/AKT/SOX2 axis

Authors 

H C JeongS J ParkJ J ChoiY H GoS K HongO S KwonJ G ShinR K KimMi Ok LeeS J LeeH D ShinS H MoonH J Cha

Publisher 

Wiley-Blackwell

Issue Date 

2017

Citation 

Stem Cells

Keywords 

Human embryonic stem cellsMesodermal differentiationPI3K-AKT pathwayPluripotencyPRMT8SOX2

Abstract 

Basic fibroblast growth factor (bFGF) supplementation is critical to maintain the pluripotency of human pluripotent stem cells (hPSCs) through activation of PI3K/AKT, rather than MEK/ERK pathway. Thus, elaborate molecular mechanisms that preserve PI3K/AKT signaling upon bFGF stimulation may exist in hPSCs. Protein arginine methyltransferase 8 (PRMT8) was expressed and then its level gradually decreased during spontaneous differentiation of human embryonic stem cells (hESCs). PRMT8 loss- or gain-of-function studies demonstrated that PRMT8 contributed to longer maintenance of hESC pluripotency, even under bFGF-deprived conditions. Direct interaction of membrane-localized PRMT8 with p85, a regulatory subunit of PI3K, was associated with accumulation of phosphoinositol 3-phosphate and consequently high AKT activity. Furthermore, the SOX2 induction, which was controlled by the PRMT8/PI3K/AKT axis, was linked to mesodermal lineage differentiation. Thus, we propose that PRMT8 in hESCs plays an important role not only in maintaining pluripotency but also in controlling mesodermal differentiation through bFGF signaling toward the PI3K/AKT/SOX2 axis. Stem Cells 2017; 35:2037?2049

ISSN 

1066-5099

Link 

http://dx.doi.org/10.1002/stem.2642

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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