Please use this identifier to cite or link to this item: https://doi.org/10.18632/oncotarget.23786
DC FieldValue
dc.titleOxidative stress promotes exit from the stem cell state and spontaneous neuronal differentiation
dc.contributor.authorHu, Q
dc.contributor.authorKhanna, P
dc.contributor.authorEe Wong, B.S
dc.contributor.authorHeng, Z.S.L
dc.contributor.authorSubhramanyam, C.S
dc.contributor.authorThanga, L.Z
dc.contributor.authorTan, S.W.S
dc.contributor.authorBaeg, G.H
dc.date.accessioned2020-09-04T02:25:31Z
dc.date.available2020-09-04T02:25:31Z
dc.date.issued2018
dc.identifier.citationHu, Q, Khanna, P, Ee Wong, B.S, Heng, Z.S.L, Subhramanyam, C.S, Thanga, L.Z, Tan, S.W.S, Baeg, G.H (2018). Oxidative stress promotes exit from the stem cell state and spontaneous neuronal differentiation. Oncotarget 9 (3) : 4223-4238. ScholarBank@NUS Repository. https://doi.org/10.18632/oncotarget.23786
dc.identifier.issn1949-2553
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/174366
dc.description.abstractReactive oxygen species (ROS) play important roles in fundamental cellular processes such as proliferation and survival. Here we investigated the effect of oxidative stress on stem cell maintenance and neuronal differentiation in a human embryonic stem cell (hESC) model, Ntera2 (NT2). CM-H2DCFDA and DHE assays confirmed that the oxidizing agent paraquat could induce a high level of ROS in NT2 cells. Quantitative PCR, Western blotting and immunocytochemistry showed that paraquat-induced oxidative stress suppressed the expression of stemness markers, including NANOG, OCT4 and TDGF1, whereas it enhanced the spontaneous expression of neuronal differentiation markers such as PAX6, NEUROD1, HOXA1, NCAM, GFRA1 and TUJ1. The treated cells even exhibited a strikingly different morphology from control cells, extending out long neurite-like processes. The neurogenic effect of ROS on stem cell behaviour was confirmed by the observations that the expression of neuronal markers in the paraquat-treated cells was suppressed by an antioxidant while further enhanced by knocking down Nrf2, a key transcription factor associated with antioxidant signaling. Lastly, paraquat dose-dependently activated the neurogenic MAPK-ERK1/2, which can be reversed by the MEK1/2 inhibitor SL327. Our study suggests that excessive intracellular ROS can trigger the exit from stem cell state and promote the neuronal differentiation of hESCs, and that MAPK-ERK1/2 signaling may play a proactive role in the ROS-induced neuronal differentiation of hESCs. © Hu et al.
dc.publisherImpact Journals LLC
dc.sourceUnpaywall 20200831
dc.subjectalpha [amino(4 aminophenylthio)methylene] 2 (trifluoromethyl)phenylacetonitrile
dc.subjectantioxidant
dc.subjectmitogen activated protein kinase
dc.subjectmitogen activated protein kinase 1
dc.subjectmitogen activated protein kinase 3
dc.subjectparaquat
dc.subjectreactive oxygen metabolite
dc.subjecttranscription factor Nrf2
dc.subjectArticle
dc.subjectcell level
dc.subjectcell structure
dc.subjectcontrolled study
dc.subjectembryo
dc.subjectembryonic stem cell
dc.subjectgene
dc.subjectgene expression
dc.subjectGFRA1 gene
dc.subjectHOXA1 gene
dc.subjecthuman
dc.subjecthuman cell
dc.subjectimmunocytochemistry
dc.subjectNANOG gene
dc.subjectNCAM gene
dc.subjectnerve cell differentiation
dc.subjectneurite
dc.subjectNEUROD1 gene
dc.subjectOCT4 gene
dc.subjectoxidative stress
dc.subjectPAX6 gene
dc.subjectpolymerase chain reaction
dc.subjectquantitative analysis
dc.subjectsignal transduction
dc.subjectTDGF1 gene
dc.subjectTUJ1 gene
dc.subjectWestern blotting
dc.typeArticle
dc.contributor.departmentANATOMY
dc.contributor.departmentDUKE-NUS MEDICAL SCHOOL
dc.contributor.departmentANATOMY
dc.description.doi10.18632/oncotarget.23786
dc.description.sourcetitleOncotarget
dc.description.volume9
dc.description.issue3
dc.description.page4223-4238
Appears in Collections:Elements
Staff Publications

Show simple item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
10_18632_oncotarget_23786.pdf4.26 MBAdobe PDF

OPEN

NoneView/Download

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.