It is well known that metastatic cancer causes the vast majority of deaths as opposed to the original tumor. However, researchers still struggle to fully understand the mechanisms of metastasis due to a lack of tools that can probe the emerging diseased cells at a high enough resolution. Drs Simeonov and Lengner at the University of Pennsylvania Perelman School of Medicine have recently built a precision tool for investigating cancer metastasis in vivo. Using a mouse model of pancreatic cancer, they developed a cell lineage recorder named “macsGESTALT”, which combines barcoding cells (via CRISPR/Cas9) with single-cell RNA sequencing. This new tool enables researchers to “recover ∼380,000 CRISPR target sites and reconstruct dissemination of ∼28,000 single cells across multiple metastatic sites”. The results of this data collection show that it’s not just genetic mutations alone causing the problem: It’s the gene expression patterns too. As a proof of concept, the researchers used their new tool to generate strains of cancer cells, inject them into the mice, and allow the cells to metastasize. What they found is that only one clone dominated all of the metastatic sites. After sequencing the clones, they uncovered a family of genes that are expressed in a way that enhances metastatic capability. This latest step in cancer research could reveal another crack in this disease’s armor to exploit. For those interested, here is the original article:

https://www.sciencedirect.com/science/article/abs/pii/S1535610821002713?via%3Dihub

On Single Cell Genetic Tracing and Metastasis

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