Genome-Wide Profiling of Transcriptome and DNA Methylome in Human Embryonic Stem Cells Exposed to Extractable Organic Matter from PM2.5
Increasing evidence indicates that PM2.5 exposure disrupts early embryonic development, but the mechanisms remain unclear. We hypothesized that PM2.5 cause abnormal embryonic development by interfering with DNA methylation and mRNA expression. In this study, we observed that human embryonic stem cel...
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MDPI AG
2023-10-01
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| Series: | Toxics |
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| Online Access: | https://www.mdpi.com/2305-6304/11/10/840 |
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| author | Jianming Wang Tiantian Liu Jin Wang Tao Chen Yan Jiang |
| author_facet | Jianming Wang Tiantian Liu Jin Wang Tao Chen Yan Jiang |
| author_sort | Jianming Wang |
| collection | DOAJ |
| description | Increasing evidence indicates that PM2.5 exposure disrupts early embryonic development, but the mechanisms remain unclear. We hypothesized that PM2.5 cause abnormal embryonic development by interfering with DNA methylation and mRNA expression. In this study, we observed that human embryonic stem cells (hESCs) treated with extractable organic matters (EOM) from PM2.5 concentrations above 100 μg/mL exhibited reduced viability. While EOM within non-cytotoxicity concentrations did not affect the expression levels of pluripotency genes, it did enhance cellular proliferation, as indicated by increased Edu incorporation and the upregulation of cell cycle genes (Cdk2, Mdm2). Additionally, EOM significantly influenced the transcriptome patterns in hESCs. Notably, the differentially expressed genes were found to be significantly enriched in processes such as extracellular matrix organization, cell–cell junction organization, chromatin organization, and DNA methylation. Furthermore, we observed whole genomic-wide DNA methylation changes. Through a cross-analysis of changes in DNA methylation and mRNA expression, we identified an enrichment of terms related to the VEGFR signaling pathway and extracellular matrix. The gene signal transduction networks revealed that crucial hubs were implicated in cell growth and division. In conclusion, our findings demonstrate that PM2.5 induce significant alterations in transcriptome and DNA methylome in hESCs, leading to aberrant cell proliferation. This research provides novel insights into the molecular mechanisms underlying the developmental toxicity of PM2.5. |
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| language | English |
| last_indexed | 2024-03-10T20:51:12Z |
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| spelling | doaj.art-b6a83349452f433986dc92466bb0de1e2023-11-19T18:21:45ZengMDPI AGToxics2305-63042023-10-01111084010.3390/toxics11100840Genome-Wide Profiling of Transcriptome and DNA Methylome in Human Embryonic Stem Cells Exposed to Extractable Organic Matter from PM2.5Jianming Wang0Tiantian Liu1Jin Wang2Tao Chen3Yan Jiang4Suzhou Medical College, Soochow University, Suzhou 215123, ChinaSuzhou Medical College, Soochow University, Suzhou 215123, ChinaSuzhou Medical College, Soochow University, Suzhou 215123, ChinaSuzhou Medical College, Soochow University, Suzhou 215123, ChinaSuzhou Medical College, Soochow University, Suzhou 215123, ChinaIncreasing evidence indicates that PM2.5 exposure disrupts early embryonic development, but the mechanisms remain unclear. We hypothesized that PM2.5 cause abnormal embryonic development by interfering with DNA methylation and mRNA expression. In this study, we observed that human embryonic stem cells (hESCs) treated with extractable organic matters (EOM) from PM2.5 concentrations above 100 μg/mL exhibited reduced viability. While EOM within non-cytotoxicity concentrations did not affect the expression levels of pluripotency genes, it did enhance cellular proliferation, as indicated by increased Edu incorporation and the upregulation of cell cycle genes (Cdk2, Mdm2). Additionally, EOM significantly influenced the transcriptome patterns in hESCs. Notably, the differentially expressed genes were found to be significantly enriched in processes such as extracellular matrix organization, cell–cell junction organization, chromatin organization, and DNA methylation. Furthermore, we observed whole genomic-wide DNA methylation changes. Through a cross-analysis of changes in DNA methylation and mRNA expression, we identified an enrichment of terms related to the VEGFR signaling pathway and extracellular matrix. The gene signal transduction networks revealed that crucial hubs were implicated in cell growth and division. In conclusion, our findings demonstrate that PM2.5 induce significant alterations in transcriptome and DNA methylome in hESCs, leading to aberrant cell proliferation. This research provides novel insights into the molecular mechanisms underlying the developmental toxicity of PM2.5.https://www.mdpi.com/2305-6304/11/10/840PM2.5human embryonic stem cellstranscriptomeDNA methylometoxicity |
| spellingShingle | Jianming Wang Tiantian Liu Jin Wang Tao Chen Yan Jiang Genome-Wide Profiling of Transcriptome and DNA Methylome in Human Embryonic Stem Cells Exposed to Extractable Organic Matter from PM2.5 Toxics PM2.5 human embryonic stem cells transcriptome DNA methylome toxicity |
| title | Genome-Wide Profiling of Transcriptome and DNA Methylome in Human Embryonic Stem Cells Exposed to Extractable Organic Matter from PM2.5 |
| title_full | Genome-Wide Profiling of Transcriptome and DNA Methylome in Human Embryonic Stem Cells Exposed to Extractable Organic Matter from PM2.5 |
| title_fullStr | Genome-Wide Profiling of Transcriptome and DNA Methylome in Human Embryonic Stem Cells Exposed to Extractable Organic Matter from PM2.5 |
| title_full_unstemmed | Genome-Wide Profiling of Transcriptome and DNA Methylome in Human Embryonic Stem Cells Exposed to Extractable Organic Matter from PM2.5 |
| title_short | Genome-Wide Profiling of Transcriptome and DNA Methylome in Human Embryonic Stem Cells Exposed to Extractable Organic Matter from PM2.5 |
| title_sort | genome wide profiling of transcriptome and dna methylome in human embryonic stem cells exposed to extractable organic matter from pm2 5 |
| topic | PM2.5 human embryonic stem cells transcriptome DNA methylome toxicity |
| url | https://www.mdpi.com/2305-6304/11/10/840 |
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