2019
DOI: 10.1016/j.stemcr.2019.08.014
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Base-Resolution Methylome of Retinal Pigment Epithelial Cells Used in the First Trial of Human Induced Pluripotent Stem Cell-Based Autologous Transplantation

Abstract: SummaryThe first-in-human trial of induced pluripotent stem cell (iPSC)-based autologous transplantation was successfully performed on a female patient with age-related macular degeneration. Here we delineated the base-resolution methylome of the iPSC-derived retinal pigment epithelium (iRPE) used in this trial. The methylome of iRPE closely resembled that of native RPE (nRPE), although partially methylated domains (PMDs) emerged in iRPE but not nRPE. Most differentially methylated regions between iRPE and nRP… Show more

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Cited by 19 publications
(18 citation statements)
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“…For the comparison between KNS-42 with and without G34V allele, we used DMRs with P-values less than 10 −5 . ICA was performed using the fastICA package in R as described previously 39 . Outputs of ICA were used to generate Euclidian distance matrices for hierarchical clustering by Ward’s method.…”
Section: Methodsmentioning
confidence: 99%
“…For the comparison between KNS-42 with and without G34V allele, we used DMRs with P-values less than 10 −5 . ICA was performed using the fastICA package in R as described previously 39 . Outputs of ICA were used to generate Euclidian distance matrices for hierarchical clustering by Ward’s method.…”
Section: Methodsmentioning
confidence: 99%
“…Previous reports have shown the importance of correct DNA methylome patterning during human iPSC reprograming towards RPE (Araki, et al, 2019), and have proved a requirement for active demethylation during eye formation in vertebrates (Xu, et al, 2012). Thus, to further characterize the NR and RPE specific DOCRs, we next interrogated their DNA methylome profiles.…”
Section: -Chromatin Accessibility In Nr Vs Rpe Precursors Identifiementioning
confidence: 99%
“…In contrast to stable imprinting associated with somatic cells, we observed many methylation aberrations at gDMRs for many of the imprinted clusters in hiPSCs (Figure 5C ; Supplementary Table S3 ). In addition to hESCs, imprinted defects have been broadly associated with hiPSCs ( 50–52 ) and are one of the major concerns for the downstream applications of these cells ( 54 , 55 ). A few of the imprinted loci showed no or minor abnormalities (e.g.…”
Section: Resultsmentioning
confidence: 99%
“…Indeed, genomic imprinting has been shown to gain distorted patterns through stem cell conditions and upon reprogramming of somatic cells into hiPSCs. This creates an epigenetic obstacle for their correct use in disease modelling and their application in regenerative medicine ( 38 , 50–52 , 54 ). In contrast to blood samples and primary dermal fibroblast, hESCs and hiPSCs exhibit several imprinting defects consistent with the reports in the literature ( Supplementary Table S4 ) ( 55 ).…”
Section: Discussionmentioning
confidence: 99%