'Invisible' cell types and gene expression revealed with sequencing data analysis improvement

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'Invisible' cell types and gene expression revealed with sequencing data analysis improvement
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In 2018, researchers in the Caltech laboratory of Yuki Oka, professor of biology and Heritage Medical Research Institute Investigator, made a major discovery: They identified a type of neuron, or brain cell, that mediates thirst satiation. But they were running into a problem: A state-of-the-art technique called single-cell RNA sequencing (scRNA-seq) could not find those thirst-related neurons in samples of brain tissue (specifically, from a region called the media preoptic nucleus) that were known to contain them.

"We knew that the gene labeling we added to our characterized neurons was being expressed in the median preoptic nucleus of the brain, but we didn't see the gene when we profiled that region of the brain with scRNA-seq," says Oka.

Though cells can differ in shape and function, most cells in a given organism contain an identical genetic blueprint—the genome. The genome contains instructions on how to do any cellular task. The genes that comprise the genome are written in DNA, located in the cell's nucleus. Expressed genes are copied into RNA, which is transported out of the nucleus and into the rest of the cell to carry out functions.

One problem with the technique, however, was that certain RNA sequencing data were commonly not included in gene-expression estimates, even though they represented expressed genes.

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