Figure 1
From: Synchrony and asynchrony between an epigenetic clock and developmental timing
(A) Development of the retina proceeds in a regular order of cell addition, with the progenitors (P, pink) first making the early cell types, ganglion cells (G, green), the horizontal cells (H, blue), and then the cones (C, orange), followed by a later phase of histogenesis where the late cell types are generated, including the amacrine cells (A, purple), the rod photoreceptors (R, orange), the bipolar cells (B, dark green), and the Müller glia (not shown). Cell genesis is followed by a regular sequence of differentiation events during which the cells elaborate dendrites and make synapses with one another. (B) Bulk RNAseq of fetal retina was organized into six superclusters to highlight gene expression trends during retinogenesis (data re-plotted from Hoshino et al.27). (C) Chronological age (x-axis) versus epigenetic age (y-axis) of cerebral cortex and fetal retina. C’. Expanded view of the correlation between DNA mAge and gestational age of fetal retinal samples. Slope = 1.235 ± 0.1676, R square = 0.8; NOTE: that the time axes are not the same between C and C’. (D). Human fetal retina exhibits characteristic central to periphery gradient, where the fovea is more accelerated than the periphery (P) at the same age. The periphery is mostly comprised of progenitors (SOX2, cyan), photoreceptors (RCVRN, magenta) and ganglion/early amacrine cells (ELAVL3/4,green) in a D96 fetal retina while fovea exhibits box-shaped cones and additional RCVRN-positive bipolars (dashed rectangle), amacrine (ELAVL3/4 in the INL) and Müller glia markers (SOX2 in INL) indicative of accelerated retinal development (DAPI in white) E. Epigenetic age remains conserved across different regions of the retina, despite their developmental differences. (ONL = Outer nuclear layer, INL = Inner nuclear layer, GCL = Ganglion cell layer, IPL: Inner plexiform layer; SC = supercluster). R2 in E = 0.8.
