Alzheimer s & Dementia | 2019
WESTERN DIET PROMOTES CENTRAL INSULIN IMPAIRMENT AND THE DYSREGULATION OF METABOLITES ASSOCIATED WITH ALZHEIMER’S DISEASE: THE ROLE OF SOLUBLE TNF
Abstract
The functionality was also evaluated using inflammation, migration and phagocytosis assays. Results: We carried out a screening using seven TFs involved in defining the microglial cell fate during embryogenesis, and identified expression of two genes to be sufficient to convert hiPSCs into induced microglia-like (iMGL) cells within 10 days. High-level expression of the main microglial markers in iMGL cells was confirmed by RT-qPCR, immunostaining and flow cytometry analyses. Quantification also revealed that our protocol yielded iMGLs of high purity. Whole transcriptome analysis demonstrated that iMGL cells resemble primary human microglia but not monocytes. Moreover, the iMGLs exhibited physiological functions, including LPS/IFNg-induced inflammatory responses, phagocytic ability and ADP/ATP-evoked signal and migration. When co-cultured with iPSC-derived neurons, iMGL cells showed an active ‘surveying’ phenotype that is dependent on a dynamic crosstalk between microglia and neurons. Conclusions: Taken together, this study established a protocol to rapidly convert hiPSCs into functional iMGL cells, which facilitates studies of humanmicroglia in disease modeling and drug discovery.