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Integrated analysis of DNA methylation and RNA transcriptome during in vitro differentiation of human pluripotent stem cells into retinal pigment epithelial cells.
- Source :
-
PloS one [PLoS One] 2014 Mar 17; Vol. 9 (3), pp. e91416. Date of Electronic Publication: 2014 Mar 17 (Print Publication: 2014). - Publication Year :
- 2014
-
Abstract
- Using the paradigm of in vitro differentiation of hESCs/iPSCs into retinal pigment epithelial (RPE) cells, we have recently profiled mRNA and miRNA transcriptomes to define a set of RPE mRNA and miRNA signature genes implicated in directed RPE differentiation. In this study, in order to understand the role of DNA methylation in RPE differentiation, we profiled genome-scale DNA methylation patterns using the method of reduced representation bisulfite sequencing (RRBS). We found dynamic waves of de novo methylation and demethylation in four stages of RPE differentiation. Integrated analysis of DNA methylation and RPE transcriptomes revealed a reverse-correlation between levels of DNA methylation and expression of a subset of miRNA and mRNA genes that are important for RPE differentiation and function. Gene Ontology (GO) analysis suggested that genes undergoing dynamic methylation changes were related to RPE differentiation and maturation. We further compared methylation patterns among human ESC- and iPSC-derived RPE as well as primary fetal RPE (fRPE) cells, and discovered that specific DNA methylation pattern is useful to classify each of the three types of RPE cells. Our results demonstrate that DNA methylation may serve as biomarkers to characterize the cell differentiation process during the conversion of human pluripotent stem cells into functional RPE cells.
- Subjects :
- Cell Adhesion
Cell Line
Cluster Analysis
Embryonic Stem Cells metabolism
Extracellular Matrix
Gene Expression Profiling
Humans
In Vitro Techniques
MicroRNAs genetics
Organ Specificity genetics
Pluripotent Stem Cells cytology
Promoter Regions, Genetic
RNA, Messenger
Cell Differentiation genetics
DNA Methylation
Epithelial Cells cytology
Epithelial Cells metabolism
Pluripotent Stem Cells metabolism
Retinal Pigment Epithelium cytology
Transcriptome
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 9
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 24638073
- Full Text :
- https://doi.org/10.1371/journal.pone.0091416