Open AccessPRMT8 Controls the Pluripotency and Mesodermal Fate of Human Embryonic Stem Cells By Enhancing the PI3K/AKT/SOX2 Axis
Author(s) -
Jeong HoChang,
Park SoonJung,
Choi JongJin,
Go YoungHyun,
Hong SoonKi,
Kwon OkSeon,
Shin JoongGon,
Kim RaeKwon,
Lee MiOk,
Lee SuJae,
Shin Hyoung Doo,
Moon SungHwan,
Cha HyukJin
Publication year - 2017
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.2642
Subject(s) - sox2 , biology , pi3k/akt/mtor pathway , microbiology and biotechnology , protein kinase b , induced pluripotent stem cell , embryonic stem cell , rex1 , stem cell , basic fibroblast growth factor , homeobox protein nanog , signal transduction , growth factor , genetics , receptor , gene
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. S tem C ells 2017;35:2037–2049