Generation and functional characterization of neuronal cells derived from iPSCs from patients with neurodegenerative diseases

Abstract

Induced pluripotent stem cells (iPSCs) are pluripotent cells derived from differentiated cells that have reacquired pluripotency through expression of specific transcription factors. The process is also referred to as cellular reprogramming. This unique method has enabled us to study diseases for which it was challenging to obtain patient samples. Due to the limitations of accessing brain samples from patients; directed differentiation of iPSC into neural subtypes affected by neurodegenerative diseases are of great value. This technology allowed us to create new in vitro models of neurodegenerative syndromes and diseases and moreover specific neural cell types that can be cultivated over long periods of time. Consequently, these techniques open up for new possibilities of regenerative medicine and drug screening platforms. We have previously successfully reprogrammed fibroblasts from human patients with Alzheimer´s Disease (AD) carrying mutations in the presenilin 1 gene (PSEN1), which is commonly mutated in familial forms of AD. In addition we have repaired the single nucleotide mutations in PSEN1 using the CRISPR/Cas9 system. Therefore, this project proposes to generate AD iPSCs-derived neurons and repaired iPSCs-derived neurons in order to compare their transcriptomic and proteomic profile.