HudsonAlpha Research Report 2021-2022

RICK MYERS

Because collecting human brain tissue from living, developing brains is not feasible, the lab has worked extensively to develop efficient cellular models of human brain cells, including from individuals with and without disease. Induced pluripotent stem cells (iPSC) are blood or skin cells that are reprogrammed to a pluripotent, stem-cell-like state. Once reprogrammed, iPS cells can be turned into any type of cell using a cocktail of sup- plements, growth factors, and proteins that mimic what naturally happens in the body. By transitioning iPSCs into neurons or other brain cells, researchers in the Myers lab can perform experiments on them, including testing drugs or other treatments. These cells help Myers’ lab transfer data gleaned from experimental models closer to human beings.

Another cutting-edge technology the Myers’ lab uses is single-cell analysis. This allows the team to study brain diseases on a cell-by-cell basis. Historically, brain sam- ples include all the cell types of the brain mixed together. If only one subtype of cell is involved in the disease pathol- ogy, its signal could be covered up by more abundant cell types. Looking at individual cells provides scientists with new, more precise information on the genetic and genomic differences between the brain of someone with a disease compared to the brain of someone without the disease. Single-cell genomics proved to be successful in the lab’s quest to identify genetic contributors to Alzheimer’s disease. The researchers used single-cell technologies to measure gene expression and DNA accessibility in

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Senior Scientist Jacob Loupe, PhD, uses the lab’s flow cytometer to isolate specific cell types from brain dissections to study how various cells regulate gene expression.

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