LPS stimulation of APOE knock-out iPSC-derived microglia with different ApoE isoforms

APOE is the main genetic modifier for late onset Alzheimer's disease (LOAD). While an APOE2/APOE3/APOE4 allelic series is well established for LOAD risk and neuropathology, molecular mechanisms underlying isoform-dependent risk and relevance of ApoE-associated lipids remain elusive. Here, we studied the effects of LPS stimulation on APOE KO iPSC-derived microglia treated with different ApoE isoforms (ApoE2/E3/E4) pre-complexed with BODIPY-cholesteryl ester (CE) and HDL -/+ recombinant LDLR extracellular domain. Overall design: LPS-stimulated APOE knock-out (KO) iPSC-derived microglia (iMG) were treated with ApoE isoforms (ApoE2/E3/E4) pre-complexed with BODIPY-CE and HDL -/+ recombinant LDLR ECD for one day prior to RNA harvest. Four different treatments were evaluated: (1) BODIPY-CE/HDL/ApoE2, (2) BODIPY-CE/HDL/ApoE3, (3) BODIPY-CE/HDL/ApoE4, (4) BODIPY-CE/HDL/ApoE4 + LDLR extracellular domain (ECD). Samples were collected from 3 independent experiments. For each of the 12 independent biological samples, two replicate sequencing libraries were prepared and analyzed.