Core E: Human iPSC Models Core
The Human iPSC models core supports other U19 projects and cores by generating a comprehensive collection of well-characterized human iPSC lines with different APOE genotypes from deeply phenotyped patients and through isogenic conversions. Human stem cells can be differentiated into cell types that secrete apoE and that are affected in disease, such as neurons, astrocytes, microglia, and vascular mural cells. These iPSC-derived cells are a powerful system for modeling the complexities of pathological gene expression and cellular phenotypes, particularly in the early phase of Alzheimers disease and other aging-related conditions. The established iPSC lines with different APOE genotypes, sex, ethnicity, and disease status will serve both this U19 and the broader scientific community to address critical gaps in our knowledge of the effects of apoE isoforms in different human brain cell types as well as 3D mini-brain cerebral organoids. Core E supports U19 Projects and Cores, and the broader scientific community by testing a critical component of the ApoE Cascade Hypothesis (ACH): to understand the effects of apoE isoforms on biochemical and cellular events leading to eventual phenotypic outcomes.