Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41598-020-72485-7
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dc.titleHigh glucose alters the DNA methylation pattern of neurodevelopment associated genes in human neural progenitor cells in vitro
dc.contributor.authorKandilya, D.
dc.contributor.authorShyamasundar, S.
dc.contributor.authorSingh, D.K.
dc.contributor.authorBanik, A.
dc.contributor.authorHande, M.P.
dc.contributor.authorSt�nkel, W.
dc.contributor.authorChong, Y.S.
dc.contributor.authorDheen, S.T.
dc.date.accessioned2021-08-24T02:42:13Z
dc.date.available2021-08-24T02:42:13Z
dc.date.issued2020
dc.identifier.citationKandilya, D., Shyamasundar, S., Singh, D.K., Banik, A., Hande, M.P., St�nkel, W., Chong, Y.S., Dheen, S.T. (2020). High glucose alters the DNA methylation pattern of neurodevelopment associated genes in human neural progenitor cells in vitro. Scientific Reports 10 (1) : 15676. ScholarBank@NUS Repository. https://doi.org/10.1038/s41598-020-72485-7
dc.identifier.issn2045-2322
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/199008
dc.description.abstractMaternal diabetes alters the global epigenetic mechanisms and expression of genes involved in neural tube development in mouse embryos. Since DNA methylation is a critical epigenetic mechanism that regulates gene functions, gene-specific DNA methylation alterations were estimated in human neural progenitor cells (hNPCs) exposed to high glucose (HG) in the present study. The DNA methylation pattern of genes involved in several signalling pathways including axon guidance (SLIT1-ROBO2 pathway), and Hippo pathway (YAP and TAZ) was altered in hNPCs exposed to HG. The expression levels of SLIT1-ROBO2 pathways genes (including its effectors, SRGAP1 and CDC42) which mediates diverse cellular processes such as proliferation, neurogenesis and axon guidance, and Hippo pathway genes (YAP and TAZ) which regulates proliferation, stemness, differentiation and organ size were downregulated in hNPCs exposed to HG. A recent report suggests a possible cross-talk between SLIT1-ROBO2 and TAZ via CDC42, a mediator of actin dynamics. Consistent with this, SLIT1 knockdown downregulated the expression of its effectors and TAZ in hNPCs, suggesting that HG perturbs the cross-talk between SLIT1-ROBO2 and TAZ in hNPCs. Overall, this study demonstrates that HG epigenetically alters the SLIT1-ROBO2 and Hippo signalling pathways in hNPCs, forming the basis for neurodevelopmental disorders in offspring of diabetic pregnancy. @ 2020, The Author(s).
dc.publisherNature Research
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceScopus OA2020
dc.typeArticle
dc.contributor.departmentDEPT OF ANATOMY
dc.contributor.departmentDEPT OF PHYSIOLOGY
dc.contributor.departmentDEPT OF OBSTETRICS & GYNAECOLOGY
dc.description.doi10.1038/s41598-020-72485-7
dc.description.sourcetitleScientific Reports
dc.description.volume10
dc.description.issue1
dc.description.page15676
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