UC San Francisco researchers have identified cells’ unique features within the developing human brain, using the latest technologies for analyzing gene activity in individual cells, and have demonstrated that large-scale cell surveys can be done much more efficiently and cheaply than was previously thought possible. Their results were published online recently in Nature Biotechnology.
“We have identified novel molecular features in diverse cell types using a new strategy of analyzing hundreds of cells individually,” says co-author Arnold Kriegstein, MD, PhD. “We expect to use this approach to help us better understand how the complexity of the human cortex arises from cells that are spun off through cell division from stem cells in the germinal region of the brain.”
The research team used technology focused on a “microfluidic” device in which individual cells are captured and flow into nano-scale chambers, where they efficiently and accurately undergo the chemical reactions needed for DNA sequencing. The research showed that the number of reading steps needed to identify and spell out unique sequences and to successfully identify cell types is 100 times fewer than had previously been assumed. The technology can be used to individually process 96 cells simultaneously.
Kriegstein says the identification of hundreds of novel biomarkers for diverse cell types will improve scientists’ understanding of the emergence of specialized neuronal subtypes. Ultimately, the combination of this new method of focusing on gene activity in single cells with other single-cell techniques involving microscopic imaging is likely to reveal the origins of developmental disorders of the brain, he adds.
The process could shed light on several brain disorders, including lissencephaly, in which the folds in the brain’s cortex fail to develop, as well as maladies diagnosed later in development, such as autism and schizophrenia. Read the article preview.
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