Genetic Variation, Not Cell Type of Origin, Underlies the Majority of Identifiable Regulatory Differences in iPSCs.
The advent of induced pluripotent stem cells (iPSCs) revolutionized human genetics by allowing us to generate pluripotent cells from easily accessible somatic tissues. This technology can have immense implications for regenerative medicine, but iPSCs also represent a paradigm shift in the study of c...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2016-01-01
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| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC4727884?pdf=render |
| _version_ | 1818178858314104832 |
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| author | Courtney K Burrows Nicholas E Banovich Bryan J Pavlovic Kristen Patterson Irene Gallego Romero Jonathan K Pritchard Yoav Gilad |
| author_facet | Courtney K Burrows Nicholas E Banovich Bryan J Pavlovic Kristen Patterson Irene Gallego Romero Jonathan K Pritchard Yoav Gilad |
| author_sort | Courtney K Burrows |
| collection | DOAJ |
| description | The advent of induced pluripotent stem cells (iPSCs) revolutionized human genetics by allowing us to generate pluripotent cells from easily accessible somatic tissues. This technology can have immense implications for regenerative medicine, but iPSCs also represent a paradigm shift in the study of complex human phenotypes, including gene regulation and disease. Yet, an unresolved caveat of the iPSC model system is the extent to which reprogrammed iPSCs retain residual phenotypes from their precursor somatic cells. To directly address this issue, we used an effective study design to compare regulatory phenotypes between iPSCs derived from two types of commonly used somatic precursor cells. We find a remarkably small number of differences in DNA methylation and gene expression levels between iPSCs derived from different somatic precursors. Instead, we demonstrate genetic variation is associated with the majority of identifiable variation in DNA methylation and gene expression levels. We show that the cell type of origin only minimally affects gene expression levels and DNA methylation in iPSCs, and that genetic variation is the main driver of regulatory differences between iPSCs of different donors. Our findings suggest that studies using iPSCs should focus on additional individuals rather than clones from the same individual. |
| first_indexed | 2024-12-11T20:54:39Z |
| format | Article |
| id | doaj.art-304b8bc7799e4e08ab21ebc25ea2a1b7 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-11T20:54:39Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-304b8bc7799e4e08ab21ebc25ea2a1b72022-12-22T00:51:09ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042016-01-01121e100579310.1371/journal.pgen.1005793Genetic Variation, Not Cell Type of Origin, Underlies the Majority of Identifiable Regulatory Differences in iPSCs.Courtney K BurrowsNicholas E BanovichBryan J PavlovicKristen PattersonIrene Gallego RomeroJonathan K PritchardYoav GiladThe advent of induced pluripotent stem cells (iPSCs) revolutionized human genetics by allowing us to generate pluripotent cells from easily accessible somatic tissues. This technology can have immense implications for regenerative medicine, but iPSCs also represent a paradigm shift in the study of complex human phenotypes, including gene regulation and disease. Yet, an unresolved caveat of the iPSC model system is the extent to which reprogrammed iPSCs retain residual phenotypes from their precursor somatic cells. To directly address this issue, we used an effective study design to compare regulatory phenotypes between iPSCs derived from two types of commonly used somatic precursor cells. We find a remarkably small number of differences in DNA methylation and gene expression levels between iPSCs derived from different somatic precursors. Instead, we demonstrate genetic variation is associated with the majority of identifiable variation in DNA methylation and gene expression levels. We show that the cell type of origin only minimally affects gene expression levels and DNA methylation in iPSCs, and that genetic variation is the main driver of regulatory differences between iPSCs of different donors. Our findings suggest that studies using iPSCs should focus on additional individuals rather than clones from the same individual.http://europepmc.org/articles/PMC4727884?pdf=render |
| spellingShingle | Courtney K Burrows Nicholas E Banovich Bryan J Pavlovic Kristen Patterson Irene Gallego Romero Jonathan K Pritchard Yoav Gilad Genetic Variation, Not Cell Type of Origin, Underlies the Majority of Identifiable Regulatory Differences in iPSCs. PLoS Genetics |
| title | Genetic Variation, Not Cell Type of Origin, Underlies the Majority of Identifiable Regulatory Differences in iPSCs. |
| title_full | Genetic Variation, Not Cell Type of Origin, Underlies the Majority of Identifiable Regulatory Differences in iPSCs. |
| title_fullStr | Genetic Variation, Not Cell Type of Origin, Underlies the Majority of Identifiable Regulatory Differences in iPSCs. |
| title_full_unstemmed | Genetic Variation, Not Cell Type of Origin, Underlies the Majority of Identifiable Regulatory Differences in iPSCs. |
| title_short | Genetic Variation, Not Cell Type of Origin, Underlies the Majority of Identifiable Regulatory Differences in iPSCs. |
| title_sort | genetic variation not cell type of origin underlies the majority of identifiable regulatory differences in ipscs |
| url | http://europepmc.org/articles/PMC4727884?pdf=render |
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