Open AccessThe Trans‐Spliced Long Noncoding RNA ts RMST Impedes Human Embryonic Stem Cell Differentiation Through WNT5A‐Mediated Inhibition of the Epithelial‐to‐Mesenchymal Transition
Author(s) -
Yu ChunYing,
Kuo HungChih
Publication year - 2016
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.2386
Subject(s) - biology , embryonic stem cell , wnt signaling pathway , microbiology and biotechnology , cellular differentiation , induced pluripotent stem cell , stem cell , gene knockdown , epithelial–mesenchymal transition , mesenchymal stem cell , transcription factor , homeobox protein nanog , signal transduction , downregulation and upregulation , genetics , cell culture , gene
The trans‐spliced noncoding RNA RMST (ts RMST ) is an emerging regulatory lncRNA in the human pluripotency circuit. Previously, we found that ts RMST represses lineage‐specific transcription factors through the PRC2 complex and NANOG in human pluripotent stem cells (hESCs). Here, we demonstrate that ts RMST also modulates noncanonical Wnt signaling to suppress the epithelial‐to‐mesenchymal transition (EMT) and in vitro differentiation of embryonic stem cells (ESCs). Our results demonstrate that disruption of ts RMST expression in hESCs results in the upregulation of WNT5A, EMT, and lineage‐specific genes/markers. Furthermore, we found that the PKC inhibitors Go6983 and Go6976 inhibited the effects of WNT5A, indicating that WNT5A promotes the EMT and in vitro differentiation although conventional and novel PKC activation in hESCs. Finally, we showed that either antiserum neutralization of WNT5A or Go6983 treatment in ts RMST knockdown cells decreased the expression of mesenchymal and lineage‐specific markers. Together, these findings indicate that ts RMST regulates Wnt and EMT signaling pathways in hESCs by repressing WNT5A, which is a potential EMT inducer for promoting in vitro differentiation of hESCs through PKC activation. Our findings provide further insights into the role of trans‐spliced RNA and WNT5A in hESC differentiation, in which EMT plays an important role. S tem C ells 2016;34:2052–2062