Project: PRJNA512519
Genome wide DNA methylation profiling of human fetal retina samples. The Illumina Infinium DNA methylation Beadchip was used to obtain DNA methylation profiles in human fetal retina samples that were cultured in different ways. To better undrestand the relationship between developmental stage and epigenetic age (measured by the Horvath clock based on 353 CpGs as detailed in pubmed identifier: 24138928), we analyzed the highly regular sequence of developmental stage in the human neural retina. Findings: epigenetic age of fetal retina is highly correlated with chronological age. We find that epigenetic aging progresses normally in vitro. The correlation is retained in stem cell derived organoids but is accelerated in individuals with Down syndrome. Overall design: We analyzed the DNA methylation patterns from the same developmental ages as the RNAseq study to evaluate DNA methylation patterns. In order to test whether the epigenetic clock continues to progress when isolated from the rest of the organism, epigenetic clock analyses were performed on explant cultures of fetal retinas from various stages of development. Explants were maintained for 3 to 6 weeks and the rate of development and the epigenetic clock was evaluated DNA methylation and RNA seq. For additional in vitro studies, we cultured retinas and showed that they progressed at approximately normal rates with respect to epigenetic age. To further test whether the aging clock is an independent property of the tissue,we asked if cells that develop completely in vitro would also follow the epigenetic clock, such as stem cell-derived retinal organoids. We derived retinal organoids from stem cells using the established protocols.