Most developing and adult tissues are hierarchically organized such that tissue growth and maintenance are driven by the production of lineage-committed cells from populations of tissue-resident stem and progenitor cells.
Stem cells in adult tissues are typically found in a quiescent or reversible G0 state and must re-enter the cell cycle and divide to promote lineage commitment. While much is known about specific regulatory events happening in organismal development and tissue homeostasis, little is known about the details of how cells enter, maintain, and exit quiescent-like states.
A team of biomedical engineering researchers developed a new cell classifier tool that takes a higher-resolution look at the life cycle of neuroepithelial stem cells, which led to the discovery and exploration of a new resting phase called Neural G0. This knowledge could help to better understand glioma brain tumors and develop new methods of treatment.
The new cell cycle classifier tool, called ccAF, or cell cycle ASU/Fred Hutchinson to represent the collaboration between institutions identifies genes that can be used to track progress through the cell cycle.
They used the ccAF tool to analyse cell data in glioma tumors and found that tumor cells were often either in the Neural G0 or G1 growth state. And as tumors become more aggressive, fewer and fewer cells remain in the resting Neural G0 state, which means that more and more cells are proliferating and growing the tumor. They correlated this data with the prognosis for patients with glioblastoma, a particularly aggressive type of brain tumor. Those with higher Neural G0 levels in tumor cells had less aggressive tumors.
One of the researchers said that quiescence itself could be a different biological process and that it is also a potential point where we could look for new drug treatments, pushing more cells into this quiescent state, the tumors would become less aggressive.
Current cancer treatments focus on killing cancer cells and after this happens, they release cell debris into the surrounding area of the tumor, which can cause the remaining cells to become more resistant to drugs. Another approach suggested by the researchers is to put the cells to sleep instead of killing them as a potentially much better option for treatment.
Figuring out what triggers a cell to enter the division cycle or remain in G0 resting state could help understand the processes behind tumor growth and is one of the current objectives of the researchers.
Arizona State University. “Sleeper cells: Newly discovered stem cell resting phase could put brain tumors to sleep: Engineering researchers discover and explore new neural stem cell state that gives insight into cancer.” ScienceDaily. ScienceDaily, 25 June 2021. www.sciencedaily.com/releases/2021/06/210625173155.htm
Samantha A O’Connor, et al. Neural G0: a quiescent‐like state found in neuroepithelial derived cells and glioma. Molecular Systems Biology, 2021; 17.