GSE110267
Human Endogenous Retrovirus-K in Stem Cell Function and Neuronal Differentiation [dataset 1]
Human endogenous retrovirus (HERV) genes were incorporated into the genome over millions of years but they mostly have inactivating mutations. HERV-K is the most recently incorporated virus. Incidental HERV-K gene expression occurs in a variety of pathological conditions. However, its physiological role is poorly understood. To study the role of HERV-K in development, we monitored its expression and function in pluripotent stem cells and during the process of neuronal differentiation. The expression of HERV-K env was localized to chromosomes 12 and 19. HERV-K Env was expressed on the cell surface of pluripotent stem cells and was critical in maintaining the stemness and adhesion of the cells. Interactions with CD98HC resulted in activation of signaling pathways that regulate stem cells genes. Down regulation of HERV-K env resulted in dissociation of the stem cell colonies and enhanced differentiation along neuronal pathways. HERV-K env expression during neurodevelopment was regulated by DNA methylation. Thus HERV-K regulation is critical for human embryonic and neurodevelopment. Overall design: Seven sample types were included: iPSC (n=3), NSC (n=3), developing neuron (NEUR) at Day 3 (n=3), developing neuron (NEUR) at Day 5 (n=3), developing neuron (NEUR) at Day 7 (n=2), developing neuron (NEUR) at Day 10 (n=3), and mature neuron (n=1).