Hangzhou Talk #5
Endogenous Retrovirus in stem cells
Endogenous Retrovirus (ERVs) belong to the transposable elements (TEs) which are epigenetically silenced in majority of cells. The reactivation of ERVs in stem cells is inflammatory. We show that the transcriptional activation of ERVs in intestinal stem cells (ISCs) leads to bowel inflammation. The dsRNA generated from ERVs binds to Z-form nucleic acids (ZNAs) sensor ZBP1 which in turn recruits RIP3 for necroptosis in ISCs. In contrast, the neuroinflammation caused by reactivation of ERVs in neural stem cells (NSCs) is independent of ZBP1 nor cell death. Neuron differentiated from those NSCs expresses higher level of Complement C4b which provokes the microglia for synaptic loss. Prenatal immune stress induces the activation of ERVs in NSCs and leads to autism. These results indicate the inflammation arisen from ERVs could be the important pathogenic factor of some intractable diseases.
