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Lung cancer cell “family trees” using CRISPR-based lineage tracking methods can reveal the course of cancer development


According to science and technology daily report, published in the “5th”Cell》A study in the journal, aInternational research teamUsing a CRISPR-based lineage tracking method, lung cancer cells were traced from the first oncogenic mutation activation, culminating in the most comprehensive lung cancer cell evolution to date, and this detailed oncology history reveals new insights into how lung cancer progresses and metastasizes.

Cancer cells can evolve to be resistant, more aggressive, and metastatic, and spread to other parts of the body to form new tumors. The more cancer evolves these traits, the more deadly it becomes. The researchers wanted to understand how cancer evolved so that it could be prevented and treated. But when cancer is discovered, it’s often in patients for years or even decades, and critical evolutionary moments have never been observed.

Jonathan Weissman and collaborators at the Whitehead Institute have developed a new way to trace generations of cancer cells, allowing researchers to analyze their evolutionary history. This lineage tracing method uses CRISPR technology to embed heritable and evolvable DNA barcodes into each cell. Each time a cell divides, its barcode is slightly modified. When the researchers finally harvested the progenitors of the original cells, they could compare the cells’ barcodes to reconstruct the “family tree” of each cell, like the evolutionary tree of the related species. The researchers used a similar approach to track the evolution of the coronavirus.

Weisman said: “This is a new way to observe cancer evolution at a higher resolution. Previously, the key events that led to tumors’ life-threatening have been opaque because they have been annihilated in the tumor’s distant past, but this provides us with a window into this history. ”

To track cancer from the start, the researchers developed a method that simultaneously triggers oncogenic mutations in cells and records the cell’s development. They engineered the mice to activate oncogenic mutations in the Kras gene when their lung cells were exposed to a special virus and inactivated the tumor suppressor gene Trp53 in the cells, while activating lineage tracing. The mouse model was engineered so that lung cancer developed in a very similar way to that in humans.

The researchers let the cancer cells evolve for several months before harvesting them. They then used a previously developed algorithm to reconstruct the cell’s genealogy from a modified DNA barcode, and also used RNA sequencing to measure gene expression in the cell to characterize the state of each cell. With this information, they can “piece together” how this type of lung cancer becomes aggressive and metastatic.

The researchers say revealing the relationships between tumor cells is key to understanding their gene expression profiles and gaining insight into the emergence of aggressive states. Get more cutting-edge research progress visit: https://byteclicks.com

In this mouse model, cancer cells develop from normal cells, and tumor progression occurs for a long time in the native environment, which means that it is very similar to what happens in human patients. For scientists, this simulation and the resulting insights are very important for cancer treatment. Because the metastasis that people fear most often occurs when cancer becomes fatal, if the evolution of cancer can be studied in detail, people can know which types of cancers will develop the ability to metastasize in what way, and thus design interventions to stop it.



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