Using NF1 Patient-Derived Induced Pluripotent Stem Cells to Investigate Mechanisms Underlying Cognitive Impairments
Abstract
Cognitive impairments are frequently experienced by NF1 patients and yet we know very little about the underlying mechanisms and how NF1 loss of function may contribute to these symptoms. Capitalizing on the discovery that adult skin fibroblasts can be reprogrammed to a state of pluripotency, we proposed to generate induced pluripotent stem cells (iPSCs) from fibroblasts of NF1 patients. We have obtained fibroblasts, performed exome sequencing of theNF1 gene for each sample, and generated several iPSC lines. We have optimized protocols to differentiate the iPSC lines to both glutamatergic and GABAergic neuronal subtypes. We did not observe any differences among NF1 patient-specific and control iPSC lines with respect to proliferation of neural progenitors or capacity to differentiate to specific neural subtypes. All differentiated lines expressed markers of synaptic development. Functional analyses revealed a potential synaptic phenotype in a subset of NF1 patient-derived glutamatergic neurons.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2019
- Accession Number
- AD1102999
Entities
Organizations
- Johns Hopkins University