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Expression data from GFP- or GFP Satellite alpha-transfected human retinal pigment epithelial cell line ARPE19

ABSTRACT: Chromatin is divided into euchromatin and heterochromatin based on differential compaction during interphase, with heterochromatin being highly condensed, existing in transcriptional inert conformation. Embedded within heterochromatin is a group of highly repetitive DNA sequences, referred to as satellite DNAs that give rise to non-coding satellite RNAs. Satellite DNA is thought to be maintained in a transcriptionally silenced state by the repressive H3K9me3 mark. However, aberrant satellite transcription can cause heterochromatin disorganization and genome instability, which have been linked to carcinogenesis. In order to study the function of heterochromatic satellite in retinal pigmental epithelia (RPE) cell, we systematically investigated transcriptome alterations in the presence of heterochromatin destabilization induced by satellite α overexpression in APRE19 cell line, a widely used human RPE cell line.

ORGANISM(S): Homo sapiens

PROVIDER: GSE100691 | GEO | 2017/07/01

SECONDARY ACCESSION(S): PRJNA392677

REPOSITORIES: GEO

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Project description:The therapeutic potential of pluripotent stem cells is great as they promise to Q7 usher in a new era of medicine where cells or organs may be prescribed to replace dysfunctional tissue. At the forefront are efforts in the eye to develop Q8 this technology as it lends itself to in vivo monitoring and sophisticated imaging modalities. In the retina, retinal pigment epithelium (RPE) is the most promising replacement cell as it has a single layer, is relatively simple to transplant, and is associated with dozens of eye diseases. However, after transplantation, they may transform and cause complications. This transformation may be partially due to incomplete maturation. With the goal of learning how to mature RPE, we compared iPSC-RPE with adult primary RPE and the immortalized ARPE-19 line. We cultured ARPE-19, iPSC-RPE, and adult human RPE for one month, evaluating morphology, RPE marker staining, and transepithelial electrical resistance as quality control indicators. We then isolated RNA for bulk RNAsequencing and DNA for genotyping. We genotyped adult RPE lines for the top age-related macular degeneration (AMD) and proliferative vitreoretinopathy (PVR) risk allele polymorphisms. Transcriptome data verified that both adult and iPSC-RPE exhibit similar RPE gene expression signatures, significantly more than ARPE-19. In addition, in iPSC-RPE, gene networks relating to epithelial to mesenchymal transition (EMT), stem cell maintenance, retina development, and muscle contraction were significantly elevated compared to those of adult RPE. We compared adult human RPE to iPSC-RPE in a model of EMT and observed an increased sensitivity of iPSC-RPE to producing contractile aggregates in vitro which resembles incident reports upon transplantation. P38 inhibition was capable of inhibiting iPSC-RPE–derived aggregates. In summary, we find that the transcriptomic signature of iPSC-RPE conveys an immature RPE state which may be ameliorated by targeting “immature” gene regulatory networks.

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Expression data from GFP- or GFP Satellite alpha-transfected human retinal pigment epithelial cell line ARPE19

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