GSE195638
Microglial APOE3 Christchurch protects neurons from Tau pathology in a human iPSC-based model of Alzheimer's disease
We generated microglia-like cells (MG) from iPSCs and fibroblast-direct reprogrammed neurons (DRNs), which preserves the aging signatures. We performed RNA seq analysis on microglia which cocultured with either old DRNs or young DRNs. By studying the microglia cocultured with DRNs, we identified CX3CL1 as the critical communication factor that is defective in the DRNs derived from old and Alzheimer's disease (AD) fibroblasts in comparison to from the young fibroblasts. Microglia displayed weakened phagocytosis activity when cocultured with old DRNs, comparing to young DRNs. The myosin-binding protein Lymphocyte-specific factor 1 (LSP1) could be a potential target of CX3CL1. The reduction of phagocytosis in old DRN MG coculture could be due to lack of LSP1 in microglia. Furthermore, supplementing the old or AD DRN-microglia coculture system with CX3CL1 ameliorated the phagocytosis defect. Overall design: Examination of RNA seq profiling of microglia which have been cocultured with the neurons directly reprogrammed from old fibroblasts and from young fibroblasts.