How the Allen Institute's new view of cell division could aid cancer research

The Allen Institute released the Integrated Mitotic Stem Cell, a data-driven model that looks at mitosis in a holistic manner. (The Allen Institute)

In 2018, the Allen Institute for Cell Science created an artificial intelligence-enabled 3D model of living human cells. Now the institution has come up with another model that offers a holistic view of mitosis, or cell division, and its researchers believe it could boost cancer research.

The new tool, called the Integrated Mitotic Stem Cell, shows 15 key cellular structures as they change shape or location, duplicate or disappear and then reassemble when cells go through the five stages of mitosis. Together, they allow scientists to examine any combination of cell structures during mitosis at the same time.

“This is the first time anyone has seen all the major parts of the cell together during mitosis,” Rick Horwitz, executive director of the Allen Institute for Cell Science, said in a statement. “Visualization of the data is critical. Once you see this process as a complete picture, you can start to uncover new, unexpected relationships and ask and answer completely new questions about cell division.”

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To develop the tool, the Allen Institute picked similarly shaped representative cells gleaned from its collection of 40,000 images for each structure in a given stage of mitosis. The result is a grid with 15 structures across the five stages.

To allow researchers to actually see those structures in human induced pluripotent stem cells, the development team added fluorescent protein tags using gene editing. In the final presentation, different components of the cells display different colors that set them apart. Confocal microscopy was used to image cells in 3D.

RELATED: Using machine learning to see inside live human cells

Even though the Allen Institute's model shows healthy cells, Horwitz argues it could also serve as the baseline for comparison with cancer cells and other abnormalities. That's because the process of cell division is highly regulated, and if anything goes wrong, diseases can result. 

When the normal control system of mitosis fails, cells can replicate and repeat the process even when it's not needed, forming cancerous cells. Scientists have observed chromosome abnormalities in cancer cells. MD Anderson scientists previously found that chromosomal changes in triple-negative breast cancer occur early on and in short bursts, rather than growing gradually over time, for example.

“To date, research on mitosis and cancer has focused mainly on chromosomes, but very few things in a cell work in isolation,” Tom Misteli, director of the National Cancer Institute’s Center for Cancer Research, said in a statement. “This new tool brings it all together, allowing researchers to connect the dots between different parts of the cell. We haven’t had that until now.”

Allen Institute researchers have already made several new observations using the tool. They noticed that all of the major changes in structure location and shapes appear to begin during early prometaphase, which is the second stage of mitosis. The organization of the structures remains largely unchanged during metaphase, which occurs right before chromosomes are separated into to daughter cells, according to the institution.

 

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