Fig. 2. COSMOC knockdown alters lipid metabolism, DNA regulation and redox homeostasis.

a Venn diagram summarizing the number of genes differentially expressed in OSCs of control subjects C1 et C2 transfected with si-COSMOC after normalization on control OSCs (n = 2). A two dimensional representation of the common dysregulated genes is visible in the heat map. b Gene ontology (GO) terms significantly enriched among differentially expressed genes in COSMOC-depleted cells. Red bars indicate the fold enrichment of the Gene Ontology (GO) and blue bars indicate the gene count. Two enriched clusters respectively enriched with genes involved in lipid and sterol metabolism or cholesterol biosynthesis and genes involved in nucleosome core, methylation and chromosome process were detected. The GO terms oxidation-reduction process and aging are not clustered or significantly enriched but represent a significant number of deregulated genes. c–e RT-qPCR validation of the transcriptome analysis. Dysregulation of a subset of genes involved in cholesterol biosynthesis process (DHCR7 INSIG1, LIPA, ACAT2 and ABCA1), redox homeostasis (GLO1 and ALDH9A1) and synaptic transmission or neural development (PTBP2, KIS and ATL3) was confirmed in OSCs deficient in COSMOC compared with cells treated with siRNA control. Highly similar results were obtained with both microarray and RT-qPCR techniques (n = 4; Mann–Whitney test: *p < 0.05). Genes known to be associated with ASD are written in green. f Quantitative analysis of oxidative stress in stem cells depleted in COSMOC, MOCOS, AOX, or XDH and comparison with cells treated with si-Control (n = 4; Mann–Whitney test: *p < 0.05). g RT-qPCR analysis of COSMOC and MOCOS expression after exposure of stem cells to H₂O₂ for 2 or 4 h (n = 4; Mann–Whitney test: *p < 0.05). For all figures, n stands for number of biological replicates of OSC.