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A Guide to Generating and Using hiPSC Derived NPCs for the Study of Neurological Diseases
Published on: February 21, 2015
Modeling complex neuropsychiatric disorders with human induced pluripotent stem cells
Brian T D Tobe1, Evan Y Snyder, Jeffrey S Nye
1Program in Stem Cell & Regenerative Biology, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037, United States.
Current Opinion in Pharmacology
|July 5, 2011
Summary
Human induced pluripotent stem cells (hiPSCs) offer a novel window into complex neuropsychiatric disorders (cNPDs), revealing cellular variations and potential therapeutic targets. Rigorous analysis is key for robust modeling of these conditions.
Area of Science:
- Neuroscience
- Stem Cell Biology
- Genetics
Background:
- Complex neuropsychiatric disorders (cNPDs) present challenges due to inaccessible neurons and diagnostic variability.
- Genetic and environmental factors interplay significantly in the etiology of cNPDs.
- Previous research has been limited by the difficulty in studying human central neurons directly.
Purpose of the Study:
- To investigate the molecular and cellular underpinnings of cNPDs using patient-derived cells.
- To explore the potential of human induced pluripotent stem cells (hiPSCs) in modeling cNPDs.
- To identify potential therapeutic targets and personalized treatment strategies for cNPD subgroups.
Main Methods:
- Utilized neuronally differentiated human induced pluripotent stem cells (hiPSCs) from individuals with Mendelian and polygenic cNPDs.
- Examined neuritic, synaptic, and cell body variations.
- Analyzed specific gene and protein expression alterations, sometimes after cellular stress or prolonged differentiation.
Main Results:
- Identified specific cellular variations and gene/protein expression changes in hiPSC models that mimic known cNPD pathology.
- Observed that some cellular phenotypes emerged only after specific stimuli or extended differentiation periods.
- Demonstrated that pathological features were responsive to pharmacological treatments, suggesting therapeutic potential.
Conclusions:
- Differentiated hiPSCs provide a valuable platform for discovering personalized therapeutics for cNPDs.
- hiPSC models can help identify pathogenetically relevant targets within specific patient subgroups.
- Statistical rigor and independent validation are crucial for robust modeling of cNPDs using hiPSC-derived 'omics' data.
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