iPSCs and iPSC-derived cells as a model of human genetic and epigenetic variation
Abstract Understanding the interaction between genetic and epigenetic variation remains a challenge due to confounding environmental factors. We propose that human induced Pluripotent Stem Cells (iPSCs) are an excellent model to study the relationship between genetic and epigenetic variation while c...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56569-4 |
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| _version_ | 1849724168341291008 |
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| author | Kara Quaid Xiaoyun Xing Yi-Hsien Chen Yong Miao Amber Neilson Vijayalingam Selvamani Aaron Tran Xiaoxia Cui Ming Hu Ting Wang |
| author_facet | Kara Quaid Xiaoyun Xing Yi-Hsien Chen Yong Miao Amber Neilson Vijayalingam Selvamani Aaron Tran Xiaoxia Cui Ming Hu Ting Wang |
| author_sort | Kara Quaid |
| collection | DOAJ |
| description | Abstract Understanding the interaction between genetic and epigenetic variation remains a challenge due to confounding environmental factors. We propose that human induced Pluripotent Stem Cells (iPSCs) are an excellent model to study the relationship between genetic and epigenetic variation while controlling for environmental factors. In this study, we have created a comprehensive resource of high-quality genomic, epigenomic, and transcriptomic data from iPSC lines and three iPSC-derived cell types (neural stem cell (NSC), motor neuron, monocyte) from three healthy donors. We find that epigenetic variation is most strongly associated with genetic variation at the iPSC stage, and that relationship weakens as epigenetic variation increases in differentiated cells. Additionally, cell type is a stronger source of epigenetic variation than genetic variation. Further, we elucidate a utility of studying epigenetic variation in iPSCs and their derivatives for identifying important loci for GWAS studies and the cell types in which they may be acting. |
| format | Article |
| id | doaj-art-a8eb526c0f144efc94e4dd49d6fbd78f |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-a8eb526c0f144efc94e4dd49d6fbd78f2025-08-20T03:10:49ZengNature PortfolioNature Communications2041-17232025-02-0116111510.1038/s41467-025-56569-4iPSCs and iPSC-derived cells as a model of human genetic and epigenetic variationKara Quaid0Xiaoyun Xing1Yi-Hsien Chen2Yong Miao3Amber Neilson4Vijayalingam Selvamani5Aaron Tran6Xiaoxia Cui7Ming Hu8Ting Wang9Center for Genome Sciences & Systems Biology, Washington University in St. LouisCenter for Genome Sciences & Systems Biology, Washington University in St. LouisGenome Engineering & Stem Cell Center (GESC@MGI), Department of Genetics, Washington University School of Medicine in St. LouisGenome Engineering & Stem Cell Center (GESC@MGI), Department of Genetics, Washington University School of Medicine in St. LouisGenome Engineering & Stem Cell Center (GESC@MGI), Department of Genetics, Washington University School of Medicine in St. LouisGenome Engineering & Stem Cell Center (GESC@MGI), Department of Genetics, Washington University School of Medicine in St. LouisCenter for Genome Sciences & Systems Biology, Washington University in St. LouisGenome Engineering & Stem Cell Center (GESC@MGI), Department of Genetics, Washington University School of Medicine in St. LouisDepartment of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic FoundationCenter for Genome Sciences & Systems Biology, Washington University in St. LouisAbstract Understanding the interaction between genetic and epigenetic variation remains a challenge due to confounding environmental factors. We propose that human induced Pluripotent Stem Cells (iPSCs) are an excellent model to study the relationship between genetic and epigenetic variation while controlling for environmental factors. In this study, we have created a comprehensive resource of high-quality genomic, epigenomic, and transcriptomic data from iPSC lines and three iPSC-derived cell types (neural stem cell (NSC), motor neuron, monocyte) from three healthy donors. We find that epigenetic variation is most strongly associated with genetic variation at the iPSC stage, and that relationship weakens as epigenetic variation increases in differentiated cells. Additionally, cell type is a stronger source of epigenetic variation than genetic variation. Further, we elucidate a utility of studying epigenetic variation in iPSCs and their derivatives for identifying important loci for GWAS studies and the cell types in which they may be acting.https://doi.org/10.1038/s41467-025-56569-4 |
| spellingShingle | Kara Quaid Xiaoyun Xing Yi-Hsien Chen Yong Miao Amber Neilson Vijayalingam Selvamani Aaron Tran Xiaoxia Cui Ming Hu Ting Wang iPSCs and iPSC-derived cells as a model of human genetic and epigenetic variation Nature Communications |
| title | iPSCs and iPSC-derived cells as a model of human genetic and epigenetic variation |
| title_full | iPSCs and iPSC-derived cells as a model of human genetic and epigenetic variation |
| title_fullStr | iPSCs and iPSC-derived cells as a model of human genetic and epigenetic variation |
| title_full_unstemmed | iPSCs and iPSC-derived cells as a model of human genetic and epigenetic variation |
| title_short | iPSCs and iPSC-derived cells as a model of human genetic and epigenetic variation |
| title_sort | ipscs and ipsc derived cells as a model of human genetic and epigenetic variation |
| url | https://doi.org/10.1038/s41467-025-56569-4 |
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