GSE43366
Defining the microglia transcriptome during disease progression in ALS transgenic mice
Purpose:  We purified spinal cord microglia utilizing percoll gradients and magnetic beads, followed by transcriptome profiling (RNA-seq) to define microglia expression profiles against other neural, immune cell-types.  We next observed how the microglai transcriptomes change during activation in the SOD1-G93A mouse model of motor neuron degeneration at 3 timepoints.  We also compared these profiles with that induced by LPS injection. Results and conclusions:  ALS microglia were found to differ substantially from those activated by LPS and from M1/M2 macrophages by comparison with published datasets. These ALS microglia showing substantial induction of a "neurodegeneration-tailored phenotype", with induction of lysosomal, RNA splicing, and Alzheimer''s disease pathway genes.  Overall they express a mixture of neuroprotective and neurotoxic factors during activation in ALS mice, showing that neuro-immune activation in the spinal cord is a double-edged sword.  We also detected the transcriptional nature of surface marker expression in microglia (CD11b, CD86, CD11c), and substantial T-cell microglia cross-talk using correlative microglia transcriptome/FACS analysis. Overall design: 42 total RNA samples from purified spinal cord microglia were subjected to paired-end RNA-sequencing.  Parallel flow cytometry data was collected from the same spinal cords.