Cells show disease-linked changes in metabolism, electrophysiology, cell adhesion, cell death
THURSDAY, July 5 (HealthDay News) -- Neural cells generated from skin cells from patients with Huntington's disease (HD), which is characterized by CAG repeat expansions, show characteristic features of the disease, including neurodegeneration, according to a study published online June 28 in Cell Stem Cell.
Clive Svendsen, Ph.D., from the Cedars-Sinai Medical Center in Los Angeles, and colleagues generated a panel of induced pluripotent stem cell (iPSC) lines from fibroblasts from healthy individuals and patients with early- and late-onset HD. These were converted to neural stem cells, then striatal-like neurons, which are mainly targeted by the disease. CAG repeat expansion expression patterns were assessed using microarray profiling.
The researchers found that only the differentiated neural cells derived from HD patients showed characteristic signs of the disease, including changes in electrophysiology, metabolism, and cell adhesion. Cells with both medium and longer CAG repeats, an indicator of more severe disease, ultimately died. Cells with longer repeats were more sensitive to cellular stressors and withdrawal of an important growth and differentiation factor.
"In conclusion, we have developed and characterized an iPSC model of HD that includes multiple lines, clones, and repeat lengths," Svendsen and colleagues write. "The utility of this model system includes elucidation of HD cellular pathogenesis, development of HD-specific biomarkers, and ultimately screening for small molecule or other therapeutic interventions."
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