Astrocytic response mediated by the CLU rs11136000 risk allele inhibits OPC proliferation and myelination in a human iPSC model

Purpose: To study whether and how CLU rs11136000 associates with Alzheimer’s disease (AD) in astrocytes and affects their function. Methods: Different genotypes of astrocytes were differentiated from human isogenic iPSCs which used CRISPR/Cas9 editing, and total RNA was isolated and sequenced. Results: We identified 271 up-regulated genes (Fold-change ≥ 2, p<0.05) versus 176 down-regulated genes (Fold-change ≤ 0.5, p<0.05). Conclusion: CLU expression and IFN response were up-regulated in C/C astrocytes. Different genotypes of astrocytes were differentiated from human isogenic iPSCs which used CRISPR/Cas9 editing, and total RNA was isolated and sequenced.