The Denham lab focuses on developing cell transplantation therapies for neurological disorders using human pluripotent stem cells. The lab has pioneered the development of lineage restriction as a novel method for controlling stem cell differentiation. Lineage restriction involves genetically restricting the pluripotent stem cell’s ability to differentiate down unwanted lineages. They achieve this by knocking out transcriptional regulators critical for specifying alternate lineages. They call these cells lineage-restricted undifferentiated stem cells (LR-USCs).
Current state-of-the-art differentiation protocols result in only a minor percentage of the transplanted cells becoming dopaminergic neurons. To address this, the lab developed LR-USCs that robustly generate mesencephalic dopaminergic neurons under a broad range of differentiation conditions. These LR-USCs efficiently and reliably generate dopaminergic neurons, making them ideal for large-scale clinical production. In addition to developing LR-USCs for Parkinson’s disease, the lab is applying this approach to create LR-USCs specialized for generating other cell types for various diseases. https://doi.org/10.1101/2021.09.28.462222
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