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Article: Hyperglycemia Altered DNA Methylation Status and Impaired Pancreatic Differentiation from Embryonic Stem Cells
Title | Hyperglycemia Altered DNA Methylation Status and Impaired Pancreatic Differentiation from Embryonic Stem Cells |
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Authors | |
Keywords | DNA methylation Human embryonic stem cell Hyperglycemia Pancreatic differentiation |
Issue Date | 2021 |
Citation | International Journal of Molecular Sciences, 2021, v. 22 n. 19, article no. 10729 How to Cite? |
Abstract | The prevalence of type 2 diabetes (T2D) is rapidly increasing across the globe. Fetal exposure to maternal diabetes was correlated with higher prevalence of impaired glucose tolerance and T2D later in life. Previous studies showed aberrant DNA methylation patterns in pancreas of T2D patients. However, the underlying mechanisms remained largely unknown. We utilized human embryonic stem cells (hESC) as the in vitro model for studying the effects of hyperglycemia on DNA methylome and early pancreatic differentiation. Culture in hyperglycemic conditions disturbed the pancreatic lineage potential of hESC, leading to the downregulation of expression of pancreatic markers PDX1, NKX6−1 and NKX6−2 after in vitro differentiation. Genome-wide DNA methylome profiling revealed over 2000 differentially methylated CpG sites in hESC cultured in hyperglycemic condition when compared with those in control glucose condition. Gene ontology analysis also revealed that the hypermethylated genes were enriched in cell fate commitment. Among them, NKX6−2 was validated and its hypermethylation status was maintained upon differentiation into pancreatic progenitor cells. We also established mouse ESC lines at both physiological glucose level (PG-mESC) and conventional hyperglycemia glucose level (HG-mESC). Concordantly, DNA methylome analysis revealed the enrichment of hypermethylated genes related to cell differentiation in HG-mESC, including Nkx6−1. Our results suggested that hyperglycemia dysregulated the epigenome at early fetal development, possibly leading to impaired pancreatic development. © 2021 by the authors. Licensee MDPI, Basel, Switzerland. |
Persistent Identifier | http://hdl.handle.net/10722/316992 |
ISSN | 2011 Impact Factor: 2.598 2020 SCImago Journal Rankings: 1.455 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Chen, CH | - |
dc.contributor.author | Huang, W | - |
dc.contributor.author | Fong, SW | - |
dc.contributor.author | Chan, C | - |
dc.contributor.author | Lee, KC | - |
dc.contributor.author | Yeung, WSB | - |
dc.contributor.author | Lee, CYL | - |
dc.date.accessioned | 2022-09-16T07:26:54Z | - |
dc.date.available | 2022-09-16T07:26:54Z | - |
dc.date.issued | 2021 | - |
dc.identifier.citation | International Journal of Molecular Sciences, 2021, v. 22 n. 19, article no. 10729 | - |
dc.identifier.issn | 1661-6596 | - |
dc.identifier.uri | http://hdl.handle.net/10722/316992 | - |
dc.description.abstract | The prevalence of type 2 diabetes (T2D) is rapidly increasing across the globe. Fetal exposure to maternal diabetes was correlated with higher prevalence of impaired glucose tolerance and T2D later in life. Previous studies showed aberrant DNA methylation patterns in pancreas of T2D patients. However, the underlying mechanisms remained largely unknown. We utilized human embryonic stem cells (hESC) as the in vitro model for studying the effects of hyperglycemia on DNA methylome and early pancreatic differentiation. Culture in hyperglycemic conditions disturbed the pancreatic lineage potential of hESC, leading to the downregulation of expression of pancreatic markers PDX1, NKX6−1 and NKX6−2 after in vitro differentiation. Genome-wide DNA methylome profiling revealed over 2000 differentially methylated CpG sites in hESC cultured in hyperglycemic condition when compared with those in control glucose condition. Gene ontology analysis also revealed that the hypermethylated genes were enriched in cell fate commitment. Among them, NKX6−2 was validated and its hypermethylation status was maintained upon differentiation into pancreatic progenitor cells. We also established mouse ESC lines at both physiological glucose level (PG-mESC) and conventional hyperglycemia glucose level (HG-mESC). Concordantly, DNA methylome analysis revealed the enrichment of hypermethylated genes related to cell differentiation in HG-mESC, including Nkx6−1. Our results suggested that hyperglycemia dysregulated the epigenome at early fetal development, possibly leading to impaired pancreatic development. © 2021 by the authors. Licensee MDPI, Basel, Switzerland. | - |
dc.language | eng | - |
dc.relation.ispartof | International Journal of Molecular Sciences | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject | DNA methylation | - |
dc.subject | Human embryonic stem cell | - |
dc.subject | Hyperglycemia | - |
dc.subject | Pancreatic differentiation | - |
dc.title | Hyperglycemia Altered DNA Methylation Status and Impaired Pancreatic Differentiation from Embryonic Stem Cells | - |
dc.type | Article | - |
dc.identifier.email | Chen, CH: andycch0@hku.hk | - |
dc.identifier.email | Fong, SW: szewan11@hku.hk | - |
dc.identifier.email | Lee, KC: chuenlee@hku.hk | - |
dc.identifier.email | Yeung, WSB: wsbyeung@hku.hk | - |
dc.identifier.email | Lee, CYL: cherielee@hku.hk | - |
dc.identifier.authority | Yeung, WSB=rp00331 | - |
dc.identifier.authority | Lee, CYL=rp00308 | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.3390/ijms221910729 | - |
dc.identifier.pmid | 34639069 | - |
dc.identifier.pmcid | PMC8509790 | - |
dc.identifier.scopus | eid_2-s2.0-85116282087 | - |
dc.identifier.hkuros | 336751 | - |
dc.identifier.volume | 22 | - |
dc.identifier.spage | article no. 10729 | - |
dc.identifier.epage | article no. 10729 | - |
dc.identifier.isi | WOS:000727475600001 | - |