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Article: Hyperglycemia impedes definitive endoderm differentiation of human embryonic stem cells by modulating histone methylation patterns

TitleHyperglycemia impedes definitive endoderm differentiation of human embryonic stem cells by modulating histone methylation patterns
Authors
Issue Date2017
PublisherSpringer Verlag. The Journal's web site is located at http://link.springer.de/link/service/journals/00441/index.htm
Citation
Cell and Tissue Research, 2017, v. 368 n. 3, p. 563-578 How to Cite?
AbstractExposure to maternal diabetes during fetal growth is a risk factor for the development of type II diabetes (T2D) in later life. Discovery of the mechanisms involved in this association should provide valuable background for therapeutic treatments. Early embryogenesis involves epigenetic changes including histone modifications. The bivalent histone methylation marks H3K4me3 and H3K27me3 are important for regulating key developmental genes during early fetal pancreas specification. We hypothesized that maternal hyperglycemia disrupted early pancreas development through changes in histone bivalency. A human embryonic stem cell line (VAL3) was used as the cell model for studying the effects of hyperglycemia upon differentiation into definitive endoderm (DE), an early stage of the pancreatic lineage. Hyperglycemic conditions significantly down-regulated the expression levels of DE markers SOX17, FOXA2, CXCR4 and EOMES during differentiation. This was associated with retention of the repressive histone methylation mark H3K27me3 on their promoters under hyperglycemic conditions. The disruption of histone methylation patterns was observed as early as the mesendoderm stage, with Wnt/β-catenin signaling being suppressed during hyperglycemia. Treatment with Wnt/β-catenin signaling activator CHIR-99021 restored the expression levels and chromatin methylation status of DE markers, even in a hyperglycemic environment. The disruption of DE development was also found in mouse embryos at day 7.5 post coitum from diabetic mothers. Furthermore, disruption of DE differentiation in VAL3 cells led to subsequent impairment in pancreatic progenitor formation. Thus, early exposure to hyperglycemic conditions hinders DE development with a possible relationship to the later impairment of pancreas specification.
Persistent Identifierhttp://hdl.handle.net/10722/247665
ISSN
2017 Impact Factor: 3.043
2015 SCImago Journal Rankings: 1.539
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorChen, CH-
dc.contributor.authorLee, CYL-
dc.contributor.authorFong, SW-
dc.contributor.authorWong, CCY-
dc.contributor.authorNg, EHY-
dc.contributor.authorYeung, WSB-
dc.date.accessioned2017-10-18T08:30:41Z-
dc.date.available2017-10-18T08:30:41Z-
dc.date.issued2017-
dc.identifier.citationCell and Tissue Research, 2017, v. 368 n. 3, p. 563-578-
dc.identifier.issn0302-766X-
dc.identifier.urihttp://hdl.handle.net/10722/247665-
dc.description.abstractExposure to maternal diabetes during fetal growth is a risk factor for the development of type II diabetes (T2D) in later life. Discovery of the mechanisms involved in this association should provide valuable background for therapeutic treatments. Early embryogenesis involves epigenetic changes including histone modifications. The bivalent histone methylation marks H3K4me3 and H3K27me3 are important for regulating key developmental genes during early fetal pancreas specification. We hypothesized that maternal hyperglycemia disrupted early pancreas development through changes in histone bivalency. A human embryonic stem cell line (VAL3) was used as the cell model for studying the effects of hyperglycemia upon differentiation into definitive endoderm (DE), an early stage of the pancreatic lineage. Hyperglycemic conditions significantly down-regulated the expression levels of DE markers SOX17, FOXA2, CXCR4 and EOMES during differentiation. This was associated with retention of the repressive histone methylation mark H3K27me3 on their promoters under hyperglycemic conditions. The disruption of histone methylation patterns was observed as early as the mesendoderm stage, with Wnt/β-catenin signaling being suppressed during hyperglycemia. Treatment with Wnt/β-catenin signaling activator CHIR-99021 restored the expression levels and chromatin methylation status of DE markers, even in a hyperglycemic environment. The disruption of DE development was also found in mouse embryos at day 7.5 post coitum from diabetic mothers. Furthermore, disruption of DE differentiation in VAL3 cells led to subsequent impairment in pancreatic progenitor formation. Thus, early exposure to hyperglycemic conditions hinders DE development with a possible relationship to the later impairment of pancreas specification.-
dc.languageeng-
dc.publisherSpringer Verlag. The Journal's web site is located at http://link.springer.de/link/service/journals/00441/index.htm-
dc.relation.ispartofCell and Tissue Research-
dc.rightsThe final publication is available at Springer via http://dx.doi.org/[insert DOI]-
dc.titleHyperglycemia impedes definitive endoderm differentiation of human embryonic stem cells by modulating histone methylation patterns-
dc.typeArticle-
dc.identifier.emailChen, CH: andycch0@hku.hk-
dc.identifier.emailLee, CYL: cherielee@hku.hk-
dc.identifier.emailFong, SW: szewan11@hku.hk-
dc.identifier.emailNg, EHY: nghye@hku.hk-
dc.identifier.emailYeung, WSB: wsbyeung@hku.hk-
dc.identifier.authorityLee, CYL=rp00308-
dc.identifier.authorityNg, EHY=rp00426-
dc.identifier.authorityYeung, WSB=rp00331-
dc.identifier.doi10.1007/s00441-017-2583-2-
dc.identifier.hkuros281733-
dc.identifier.volume368-
dc.identifier.issue3-
dc.identifier.spage563-
dc.identifier.epage578-
dc.identifier.isiWOS:000401328400011-
dc.publisher.placeGermany-

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