Phenotyping Neurodegeneration in Human iPSCs

Abstract

Induced pluripotent stem cell (iPSC) technology holds promise for modeling neurodegenerative diseases. Traditional approaches for disease modeling using animal and cellular models require knowledge of disease mutations. However, many patients with neurodegenerative diseases do not have a known genetic cause. iPSCs offer a way to generate patient-specific models and study pathways of dysfunction in an in vitro setting in order to understand the causes and subtypes of neurodegeneration. Furthermore, iPSC-based models can be used to search for candidate therapeutics using high-throughput screening. Here we review how iPSC-based models are currently being used to further our understanding of neurodegenerative diseases, as well as discuss their challenges and future directions.

Keywords: iPSC; neurodegeneration; omics; phenotype.

Figure 1. Studying neurodegenerative diseases using iPSC models.

(a) Somatic cells from patients are reprogrammed into iPSCs which are then differentiated into patient-specific brain cells. (b) Cells undergo cellular and molecular phenotyping. (c) These phenotypes are used for downstream analyses and high-throughput screening. (d) Results of these experiments are used to derive insights into patient subgroups, disease mechanisms, and candidate therapeutics, ultimately leading to new hypotheses for further testing.