Gene expression signatures affected by alcohol-induced DNA methylomic deregulation in human embryonic stem cells
| Autor: | Igor Spigelman, Michael Hoang, Yong Kim, Steve Horvath, Hyun-Sung Kim, Catherine Vu, Omar Khalid, Omid Elie, Jeffrey J. Kim, Thanh G. Tu, Connie Lee |
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| Rok vydání: | 2013 |
| Předmět: |
endocrine system
Cellular differentiation Gene Expression Biology Medical and Health Sciences Article Transcriptome 03 medical and health sciences 0302 clinical medicine Gene expression mental disorders Humans Gene Regulatory Networks Gene reproductive and urinary physiology Embryonic Stem Cells 030304 developmental biology Medicine(all) 0303 health sciences Ethanol Gene Expression Profiling Cell Differentiation Cell Biology General Medicine Biological Sciences DNA Methylation Embryonic stem cell Molecular biology 3. Good health Cell biology Gene expression profiling DNA methylation Stem cell 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Stem cell research, vol 12, iss 3 Khalid, O; Kim, JJ; Kim, HS; Hoang, M; Tu, TG; Elie, O; et al.(2014). Gene expression signatures affected by alcohol-induced DNA methylomic deregulation in human embryonic stem cells. Stem Cell Research, 12(3), 791-806. doi: 10.1016/j.scr.2014.03.009. UCLA: Retrieved from: http://www.escholarship.org/uc/item/2497k0c9 |
| ISSN: | 1876-7753 |
| Popis: | Stem cells, especially human embryonic stem cells (hESCs), are useful models to study molecular mechanisms of human disorders that originate during gestation. Alcohol (ethanol, EtOH) consumption during pregnancy causes a variety of prenatal and postnatal disorders collectively referred to as fetal alcohol spectrum disorders (FASDs). To better understand the molecular events leading to FASDs, we performed a genome-wide analysis of EtOH's effects on the maintenance and differentiation of hESCs in culture. Gene Co-expression Network Analysis showed significant alterations in gene profiles of EtOH-treated differentiated or undifferentiated hESCs, particularly those associated with molecular pathways for metabolic processes, oxidative stress, and neuronal properties of stem cells. A genome-wide DNA methylome analysis revealed widespread EtOH-induced alterations with significant hypermethylation of many regions of chromosomes. Undifferentiated hESCs were more vulnerable to EtOH's effect than their differentiated counterparts, with methylation on the promoter regions of chromosomes 2, 16 and 18 in undifferentiated hESCs most affected by EtOH exposure. Combined transcriptomic and DNA methylomic analysis produced a list of differentiation-related genes dysregulated by EtOH-induced DNA methylation changes, which likely play a role in EtOH-induced decreases in hESC pluripotency. DNA sequence motif analysis of genes epigenetically altered by EtOH identified major motifs representing potential binding sites for transcription factors. These findings should help in deciphering the precise mechanisms of alcohol-induced teratogenesis. © 2014 Published by Elsevier B.V. |
| Databáze: | OpenAIRE |
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