Persistent donor cell gene expression among human induced pluripotent stem cells contributes to differences with human embryonic stem cells.

Human induced pluripotent stem cells (hiPSCs) generated by de-differentiation of adult somatic cells offer potential solutions for the ethical issues surrounding human embryonic stem cells (hESCs), as well as their immunologic rejection after cellular transplantation. However, although hiPSCs have b...

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Main Authors: Zhumur Ghosh, Kitchener D Wilson, Yi Wu, Shijun Hu, Thomas Quertermous, Joseph C Wu
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2010-02-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0008975&type=printable
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author Zhumur Ghosh
Kitchener D Wilson
Yi Wu
Shijun Hu
Thomas Quertermous
Joseph C Wu
author_facet Zhumur Ghosh
Kitchener D Wilson
Yi Wu
Shijun Hu
Thomas Quertermous
Joseph C Wu
author_sort Zhumur Ghosh
collection DOAJ
description Human induced pluripotent stem cells (hiPSCs) generated by de-differentiation of adult somatic cells offer potential solutions for the ethical issues surrounding human embryonic stem cells (hESCs), as well as their immunologic rejection after cellular transplantation. However, although hiPSCs have been described as "embryonic stem cell-like", these cells have a distinct gene expression pattern compared to hESCs, making incomplete reprogramming a potential pitfall. It is unclear to what degree the difference in tissue of origin may contribute to these gene expression differences. To answer these important questions, a careful transcriptional profiling analysis is necessary to investigate the exact reprogramming state of hiPSCs, as well as analysis of the impression, if any, of the tissue of origin on the resulting hiPSCs. In this study, we compare the gene profiles of hiPSCs derived from fetal fibroblasts, neonatal fibroblasts, adipose stem cells, and keratinocytes to their corresponding donor cells and hESCs. Our analysis elucidates the overall degree of reprogramming within each hiPSC line, as well as the "distance" between each hiPSC line and its donor cell. We further identify genes that have a similar mode of regulation in hiPSCs and their corresponding donor cells compared to hESCs, allowing us to specify core sets of donor genes that continue to be expressed in each hiPSC line. We report that residual gene expression of the donor cell type contributes significantly to the differences among hiPSCs and hESCs, and adds to the incompleteness in reprogramming. Specifically, our analysis reveals that fetal fibroblast-derived hiPSCs are closer to hESCs, followed by adipose, neonatal fibroblast, and keratinocyte-derived hiPSCs.
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spelling doaj-art-75909d66e7aa40beb94fbd694c94d9332025-08-20T03:07:40ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-02-0152e897510.1371/journal.pone.0008975Persistent donor cell gene expression among human induced pluripotent stem cells contributes to differences with human embryonic stem cells.Zhumur GhoshKitchener D WilsonYi WuShijun HuThomas QuertermousJoseph C WuHuman induced pluripotent stem cells (hiPSCs) generated by de-differentiation of adult somatic cells offer potential solutions for the ethical issues surrounding human embryonic stem cells (hESCs), as well as their immunologic rejection after cellular transplantation. However, although hiPSCs have been described as "embryonic stem cell-like", these cells have a distinct gene expression pattern compared to hESCs, making incomplete reprogramming a potential pitfall. It is unclear to what degree the difference in tissue of origin may contribute to these gene expression differences. To answer these important questions, a careful transcriptional profiling analysis is necessary to investigate the exact reprogramming state of hiPSCs, as well as analysis of the impression, if any, of the tissue of origin on the resulting hiPSCs. In this study, we compare the gene profiles of hiPSCs derived from fetal fibroblasts, neonatal fibroblasts, adipose stem cells, and keratinocytes to their corresponding donor cells and hESCs. Our analysis elucidates the overall degree of reprogramming within each hiPSC line, as well as the "distance" between each hiPSC line and its donor cell. We further identify genes that have a similar mode of regulation in hiPSCs and their corresponding donor cells compared to hESCs, allowing us to specify core sets of donor genes that continue to be expressed in each hiPSC line. We report that residual gene expression of the donor cell type contributes significantly to the differences among hiPSCs and hESCs, and adds to the incompleteness in reprogramming. Specifically, our analysis reveals that fetal fibroblast-derived hiPSCs are closer to hESCs, followed by adipose, neonatal fibroblast, and keratinocyte-derived hiPSCs.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0008975&type=printable
spellingShingle Zhumur Ghosh
Kitchener D Wilson
Yi Wu
Shijun Hu
Thomas Quertermous
Joseph C Wu
Persistent donor cell gene expression among human induced pluripotent stem cells contributes to differences with human embryonic stem cells.
PLoS ONE
title Persistent donor cell gene expression among human induced pluripotent stem cells contributes to differences with human embryonic stem cells.
title_full Persistent donor cell gene expression among human induced pluripotent stem cells contributes to differences with human embryonic stem cells.
title_fullStr Persistent donor cell gene expression among human induced pluripotent stem cells contributes to differences with human embryonic stem cells.
title_full_unstemmed Persistent donor cell gene expression among human induced pluripotent stem cells contributes to differences with human embryonic stem cells.
title_short Persistent donor cell gene expression among human induced pluripotent stem cells contributes to differences with human embryonic stem cells.
title_sort persistent donor cell gene expression among human induced pluripotent stem cells contributes to differences with human embryonic stem cells
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0008975&type=printable
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AT yiwu persistentdonorcellgeneexpressionamonghumaninducedpluripotentstemcellscontributestodifferenceswithhumanembryonicstemcells
AT shijunhu persistentdonorcellgeneexpressionamonghumaninducedpluripotentstemcellscontributestodifferenceswithhumanembryonicstemcells
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