The resting phase of newly discovered stem cells could numb brain tumors

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In analyzing brain stem cell data, Assistant Professor Christopher Plaisier and PhD student in biomedical engineering Samantha O’Connor saw the phases of the cell cycle plotted in more detail than was previously possible: the rest phases of G0, including a new separate phase they called neuronal G0, in addition to the G1 and G2 growth phases, copying the S phase and dividing the M phase. Credit: Christopher Plaisier / ASU

Christopher Plaisier, assistant professor of biomedical engineering at Ira A. Fulton School of Engineering at Arizona State University, and Samantha O’Connor, a doctoral student in biomedical engineering at Plaisier Lab, lead the research for a new life cycle stem cell stage that could be the key to unlocking new methods of treating brain cancer. His work was recently published in the research journal Molecular systems biology.

“The file it is something so well studied, and yet we re-examine it for the umpteenth time, and a new phase appears to us, “says Plaisier.” Biology always has new knowledge to show us, you just have to look at it. “

The spark for this discovery came through a collaboration with Patrick Paddison, an associate professor at the Fred Hutchinson Cancer Research Center in Seattle, and Dr. Anoop Patel, an assistant professor of neurological surgery at the University of Washington who also participates in the Cold Hutchinson Cancer Research Center.

Paddison’s team asked Plaisier to help analyze data from his brain stem cells characterized by a process called monocellular RNA sequencing.

“These data turned out to be pretty surprising,” Plaisier says. “It was assigned to this beautiful circular pattern that we identified as all the different phases of the cell cycle.”

O’Connor developed a new cell cycle classifier tool (CCAF, or ASU / Fred Hutchinson cell cycle to represent collaboration between the two institutions) that has a closer look at “high resolution” than it is happening within the stem growth cycles. cells and identifies genes that can be used to track progress through the cell cycle.

“Our classifier delves into the cell cycle because there may be pieces we capture that have important implications for the disease,” O’Connor says.

When Plaisier and O’Connor used the ccAF tool to analyze glioma tumor cell data, they found the they were often in the G0 or G1 neuronal growth state. And as tumors become more aggressive, fewer and fewer cells remain in the resting Neural G0 state. This means that more and more cells are proliferating and growing .

They correlated these data with the prognosis of patients with glioblastoma, a particularly aggressive type of brain tumor. Those with higher neuronal G0 levels in tumor cells had less aggressive tumors.

They also found that the resting neuronal G0 state is independent of the rate of proliferation of a tumor, or the rate at which its cells divide and create new cells.

“This was an interesting finding from our results, that stillness in itself could be a different biological process,” says Plaisier. “It’s also a potential point where we could look for new drug treatments. If we could push more cells into this resting state, tumors would be less aggressive.”

Current treatments with cancer drugs focus on killing cancer cells. However, when cancer cells are killed, they release cell debris into the surrounding area of ​​the tumor, which can make the remaining cells more drug-resistant.

“So instead of killing the cells, if we put them to sleep, it could be a much better situation,” Plaisier says.

With their ccAF tool, they were also able to find new states at the beginning and end of the cell cycle that exist among the best-known states. These are some of the topics of your next research phase.

“We are beginning to think of ways to go deeper and learn more about the biology of the entry and exit of the cell cycle because they are potentially really important points where cells will move to the G1 or G0 state,” he said. affirm Plaisier says.

Find out what causes a cell to enter division or remaining at rest G0 could help to understand the processes behind tumor growth.

“The main feature of any cancer is that proliferate, “says Plaisier.” If we could go in there and find out what the mechanisms are, it could be a place to slow them down. “

Plaisier and O’Connor manufacture the ccAF classification tool open source and is available in a variety of formats for anyone studying single-cell RNA sequencing data to facilitate the process of studying cell cycles.


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More information:
Samantha A O’Connor et al, G0 Neural: a similar state found in neuroepithelial-derived cells and gliomas, Molecular systems biology (2021). DOI: 10.15252 / msb.20209522

Citation: Sleeping cells: the newly discovered stem cell resting phase could put brain tumors to sleep (2021, June 26) recovered on June 26, 2021 at https://medicalxpress.com/news/2021- 06-sleeper-cells-newly-stem-cell .html

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