Rho Kinase Inhibition Is Essential During In Vitro Neurogenesis and Promotes Phenotypic Rescue of Human Induced Pluripotent Stem Cell-Derived Neurons With Oligophrenin-1 Loss of Function

This study analyzed the morphological, biochemical, and functional features of OPHN1-deficient h-iPSCs and their rescue by treatment with the ROCK inhibitor fasudil, shedding light on the relevance of the ROCK pathway during neuronal differentiation and providing a neuronal model for human OPHN1 syndrome and its treatment. Significance The analysis of the levels of rho kinase (ROCK) activity at different stages of in vitro neurogenesis of human induced pluripotent stem cells reveals that ROCK activity decreases progressively in parallel with the appearance of neuronal-like morphology and upregulation of nuclear receptor NR4A1. These results shed light on the role of the ROCK pathway during early stages of human neurogenesis and provide a neuronal stem cell-based model for the treatment of OPHN1 syndrome and other neurological disorders due to ROCK dysfunction.
Source: Stem Cells Translational Medicine - Category: Stem Cells Authors: Tags: Pluripotent Stem Cells, Pluripotent Stem Cells Source Type: research