Retinal Cell Type DNA Methylation and Histone Modifications Predict Reprogramming Efficiency and Retinogenesis in 3D Organoid Cultures
Summary: Diverse cell types can be reprogrammed into pluripotent stem cells by ectopic expression of Oct4 (Pou5f1), Klf4, Sox3, and Myc. Many of these induced pluripotent stem cells (iPSCs) retain memory, in terms of DNA methylation and histone modifications (epigenetic memory), of their cellular or...
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doaj-32826e1ff45b444b95904cbff6ba595c2020-11-24T21:14:45ZengElsevierCell Reports2211-12472018-03-01221026012614Retinal Cell Type DNA Methylation and Histone Modifications Predict Reprogramming Efficiency and Retinogenesis in 3D Organoid CulturesLu Wang0Daniel Hiler1Beisi Xu2Issam AlDiri3Xiang Chen4Xin Zhou5Lyra Griffiths6Marc Valentine7Abbas Shirinifard8András Sablauer9Suresh Thiagarajan10Marie-Elizabeth Barabas11Jiakun Zhang12Dianna Johnson13Sharon Frase14Michael A. Dyer15Department of Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USADepartment of Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USADepartment of Computational Biology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USADepartment of Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USADepartment of Computational Biology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USADepartment of Computational Biology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USADepartment of Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USACytogenetics Shared Resource, St. Jude Children’s Research Hospital, Memphis, TN 38105, USADepartment of Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USADepartment of Diagnostic Imaging, St. Jude Children’s Research Hospital, Memphis, TN 38105, USADepartment of Diagnostic Imaging, St. Jude Children’s Research Hospital, Memphis, TN 38105, USADepartment of Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USADepartment of Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USADepartment of Ophthalmology, University of Tennessee Health Science Center, Memphis, TN 38163, USACell and Tissue Imaging Shared Resource, St. Jude Children’s Research Hospital, Memphis, TN 38105, USADepartment of Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA; Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, TN 38163, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; Corresponding authorSummary: Diverse cell types can be reprogrammed into pluripotent stem cells by ectopic expression of Oct4 (Pou5f1), Klf4, Sox3, and Myc. Many of these induced pluripotent stem cells (iPSCs) retain memory, in terms of DNA methylation and histone modifications (epigenetic memory), of their cellular origins, and this may bias subsequent differentiation. Neurons are difficult to reprogram, and there has not been a systematic side-by-side characterization of reprogramming efficiency or epigenetic memory across different neuronal subtypes. Here, we compare reprogramming efficiency of five different retinal cell types at two different stages of development. Retinal differentiation from each iPSC line was measured using a quantitative standardized scoring system called STEM-RET and compared to the epigenetic memory. Neurons with the lowest reprogramming efficiency produced iPSC lines with the best retinal differentiation and were more likely to retain epigenetic memory of their cellular origins. In addition, we identified biomarkers of iPSCs that are predictive of retinal differentiation. : Wang et al. reprogram retinal cell types into iPSCs and test their ability to make retinal organoids. They discover an inverse correlation between reprogramming efficiency and retinal differentiation linked to DNA/chromatin modifications and nuclear organization. These data identify molecular markers of iPSC lines that are efficient at producing retina. Keywords: iPSCs, epigenetics, reprogramming, retina, epigenetic memory, retinal organoid, chromHMM, Meis1http://www.sciencedirect.com/science/article/pii/S2211124718301396 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lu Wang Daniel Hiler Beisi Xu Issam AlDiri Xiang Chen Xin Zhou Lyra Griffiths Marc Valentine Abbas Shirinifard András Sablauer Suresh Thiagarajan Marie-Elizabeth Barabas Jiakun Zhang Dianna Johnson Sharon Frase Michael A. Dyer |
spellingShingle |
Lu Wang Daniel Hiler Beisi Xu Issam AlDiri Xiang Chen Xin Zhou Lyra Griffiths Marc Valentine Abbas Shirinifard András Sablauer Suresh Thiagarajan Marie-Elizabeth Barabas Jiakun Zhang Dianna Johnson Sharon Frase Michael A. Dyer Retinal Cell Type DNA Methylation and Histone Modifications Predict Reprogramming Efficiency and Retinogenesis in 3D Organoid Cultures Cell Reports |
author_facet |
Lu Wang Daniel Hiler Beisi Xu Issam AlDiri Xiang Chen Xin Zhou Lyra Griffiths Marc Valentine Abbas Shirinifard András Sablauer Suresh Thiagarajan Marie-Elizabeth Barabas Jiakun Zhang Dianna Johnson Sharon Frase Michael A. Dyer |
author_sort |
Lu Wang |
title |
Retinal Cell Type DNA Methylation and Histone Modifications Predict Reprogramming Efficiency and Retinogenesis in 3D Organoid Cultures |
title_short |
Retinal Cell Type DNA Methylation and Histone Modifications Predict Reprogramming Efficiency and Retinogenesis in 3D Organoid Cultures |
title_full |
Retinal Cell Type DNA Methylation and Histone Modifications Predict Reprogramming Efficiency and Retinogenesis in 3D Organoid Cultures |
title_fullStr |
Retinal Cell Type DNA Methylation and Histone Modifications Predict Reprogramming Efficiency and Retinogenesis in 3D Organoid Cultures |
title_full_unstemmed |
Retinal Cell Type DNA Methylation and Histone Modifications Predict Reprogramming Efficiency and Retinogenesis in 3D Organoid Cultures |
title_sort |
retinal cell type dna methylation and histone modifications predict reprogramming efficiency and retinogenesis in 3d organoid cultures |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2018-03-01 |
description |
Summary: Diverse cell types can be reprogrammed into pluripotent stem cells by ectopic expression of Oct4 (Pou5f1), Klf4, Sox3, and Myc. Many of these induced pluripotent stem cells (iPSCs) retain memory, in terms of DNA methylation and histone modifications (epigenetic memory), of their cellular origins, and this may bias subsequent differentiation. Neurons are difficult to reprogram, and there has not been a systematic side-by-side characterization of reprogramming efficiency or epigenetic memory across different neuronal subtypes. Here, we compare reprogramming efficiency of five different retinal cell types at two different stages of development. Retinal differentiation from each iPSC line was measured using a quantitative standardized scoring system called STEM-RET and compared to the epigenetic memory. Neurons with the lowest reprogramming efficiency produced iPSC lines with the best retinal differentiation and were more likely to retain epigenetic memory of their cellular origins. In addition, we identified biomarkers of iPSCs that are predictive of retinal differentiation. : Wang et al. reprogram retinal cell types into iPSCs and test their ability to make retinal organoids. They discover an inverse correlation between reprogramming efficiency and retinal differentiation linked to DNA/chromatin modifications and nuclear organization. These data identify molecular markers of iPSC lines that are efficient at producing retina. Keywords: iPSCs, epigenetics, reprogramming, retina, epigenetic memory, retinal organoid, chromHMM, Meis1 |
url |
http://www.sciencedirect.com/science/article/pii/S2211124718301396 |
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