Project description: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.

2020-03-12 | GSE124568 | GEO

Synchrony and asynchrony between an epigenetic clock and developmental timing [450K array]

2020-03-12 | GSE124567 | GEO

Synchrony and asynchrony between an epigenetic clock and developmental timing [RNA-Seq]

Project description:Epigenetic changes have been used to estimate chronological age across the lifespan, and some studies suggest that epigenetic "aging" clocks may already operate in developing tissue. To better understand the relationship between developmental stage and epigenetic age, we utilized the highly regular sequence of development found in the mammalian neural retina and a well-established epigenetic aging clock based on DNA methylation. Our results demonstrate that the epigenetic age of fetal retina is highly correlated with chronological age. We further establish that epigenetic aging progresses normally in vitro, suggesting that epigenetic aging is a property of individual tissues. This correlation is also retained in stem cell-derived retinal organoids, but is accelerated in individuals with Down's syndrome, a progeroid-like condition. Overall, our results suggest that epigenetic aging begins as early as a few weeks post-conception, in fetal tissues, and the mechanisms underlying the phenomenon of epigenetic aging might be studied in developing organs.

2021-01-21 | GSE124252 | GEO

Synchrony and asynchrony between an epigenetic clock and developmental timing.

Project description:Epigenetic changes have been used to estimate chronological age across the lifespan, and some studies suggest that epigenetic "aging" clocks may already operate in developing tissue. To better understand the relationship between developmental stage and epigenetic age, we utilized the highly regular sequence of development found in the mammalian neural retina and a well-established epigenetic aging clock based on DNA methylation. Our results demonstrate that the epigenetic age of fetal retina is highly correlated with chronological age. We further establish that epigenetic aging progresses normally in vitro, suggesting that epigenetic aging is a property of individual tissues. This correlation is also retained in stem cell-derived retinal organoids, but is accelerated in individuals with Down syndrome, a progeroid-like condition. Overall, our results suggest that epigenetic aging begins as early as a few weeks post-conception, in fetal tissues, and the mechanisms underlying the phenomenon of epigenetic aging might be studied in developing organs.

| S-EPMC6403397 | biostudies-literature

Synchrony and asynchrony between an epigenetic clock and developmental timing

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-03-12 | GSE124569 | GEO

Circadian clock regulation of developmental time in the kidney

Project description:We report the emergence of an endogenous circadian clock in mouse fetal kidney that regulates organogenesis. We detect circadian rhythms both in vivo with transcriptional profiling and ex vivo by bioluminescence. High-resolution structural analysis of embryonic explants reveals that global or local clock disruption results in defects that resemble human congenital abnormalities of the kidney. The onset of fetal rhythms strongly correlates with the timing of a distinct transition in branching and growth rates during a gestational window of high fetal growth demands. Defects in clock mutants typically have been attributed to accelerated aging, however, our study establishes a role for the fetal circadian clock as a developmental timer that regulates the pathways that control organogenesis, branching rate and nephron number, and thus plays a fundamental role in kidney development.

2020-04-11 | GSE148475 | GEO

Dopamine and GPCR-mediated modulation of DN1 clock neurons gates the circadian timing of sleep

Project description:The metronome-like circadian regulation of sleep timing must still adapt to an uncertain environment. Recent studies in Drosophila indicate that neuromodulation not only plays a key role in clock neuron synchronization but also affects interactions between the clock network and brain sleep centers. We show here that the targets of neuromodulators, G-Protein Coupled Receptors (GPCRs), are highly enriched in the fly brain circadian clock network. Single cell sequencing indicates that they are not only enriched, but they are also differentially expressed and contribute to clock neuron identity. We generated a comprehensive guide library to mutagenize individual GPCRs in specific neurons and verified the strategy by introducing a targeted sequencing approach. Combined with a behavioral screen, the mutagenesis strategy revealed a novel role of dopamine in sleep regulation by identifying two dopamine receptors and a clock neuron subpopulation that gate the timing of sleep.

2022-05-09 | GSE202407 | GEO

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