E2F1 orchestrates transcriptomics and oxidative metabolism in Wharton’s jelly derived mesenchymal stem cells from growth-restricted neonates

Wharton’s jelly derived Mesenchymal Stem Cells (MSCs) isolated from newborns with intrauterine fetal growth restriction were previously shown to exert anabolic features including insulin hypersensitivity. Here, we extend these observations and demonstrate that MSCs from small for gestational age (SGA) individuals have decreased mitochondrial oxygen consumption rates. Comparing normally grown and SGA MSCs using next generation sequencing studies, we measured global transcriptomic and epigenetic profiles and identified in SGA, E2F1 as an over-expressed transcription factor regulating oxidative metabolism. We further show that E2F1 regulates the differential transcriptome found in SGA and is associated with the activating histone marks H3K27ac and H3K4me3. One of the key genes regulated by E2F1 was found to be the fatty acid elongase ELOVL2, a gene involved in the endogenous synthesis of docosahexaenoic acid (DHA). ChIP-seq of E2F1, H3K27ac, H3K27me3, H3K36me3, H3K4me1 and H3K4me3 in MSCs from 3 AGA and 3 SGA samples. RNA-seq of basal, siCTRL and siE2F1 conditions in the same 6 MSC lines.