In situ single cell RNA-seq to build a 3D trascriptional map of the brain

Do you remember the results from the Connectome project mapping the connections in the human brain   and resulting in those beautiful images of wired colorful brains? Probably in the next 5 years we would get much further in the understanding of cells spatial organization in the brain!

A team from the University of California, San Diego, has recently won a five-year $9.3 million dollar from NIH to perform RNA-seq on 10,000 single neuron cells and reconstruct a 3D map of gene activity in the brain. The team plan to perform complete RNA-Seq, not just poly-A RNAs, on such a large amount of cells to get a complete picture of the high genetic variability of neuron cells sub-population.


What impress me the most (and almost sounds like science fiction to me) is the idea to apply an in situ RNA-seq protocol to reconstruct the expression profile of 500 genes. These profiles will act as a "fingerprint" for transcriptional location so that for any other whole transcriptome dataset from an isolated cell authors can look at these 500 genes to find the matched pattern and infer the brain localization of the sequenced cell.
The in situ RNA-seq protocol is fascinating itself. It's based on a technique developed by George Church's group at Harvard, which imply a chemical reaction to create pores on the cells, followed by the application of a customized microfluidic device to deposit sequencing reagents into the cell. The sequencing will take place within the tissue and the signal will be read out with a microscope.
The team leader Kun Zhang, an associate professor at UCSD's Department of Bioengineering and Institute for Genomic Medicine, anticipated that the group would spend the first two to three years developing and optimizing this protocol, while canonical sequencing will be conducted at Illumina.

A deeper coverage of the story on this post from GenomeWeb or see the news directly from UCSD press.