Phenotypical Differences in Neuronal Cultures Derived via Reprogramming the Fibroblasts from Patients Carrying Mutations in Parkinsonian Genes LRRK2 and PARK2

摘要

Fibroblasts isolated from skin biopsy specimens from patients with genetic forms of Parkinson's disease, carriers of mutations in LRRK2 and PARK2 genes, and from a healthy volunteer were reprogrammed using lentiviral vectors into induced pluripotent stem cells (iPSC). iPSC were differentiated into neuron-like cells using a cocktail of differentiation factors (N2, B27, and Noggin). The iPSC lines derived from patients with different mutations and from a healthy volunteer cultured under the same conditions were characterized by different proportion of neuronal precursors and differentiated neurons. Control Po2 line contained 56% precursors, while B15 line with LRRK2 gene mutation (G2019S) contained 35% precursor cells. Similar regularities were characteristic of Tr5 culture carrying compound heterozygous mutations in PARK2 gene (del202-203AG and IVS1+1G/A) and containing 4% neuronal precursors. Further comparative studies of iPSC carrying various mutations and comparison with normal human cells will help to understand the molecular pathogenesis of some genetic variants of Parkinson's disease.