Communication between cells is now believed to activate a memory mechanism that sustains gene expression, a finding based on the work of Dr. Gregory Reeves.
Reeves, an associate professor in the Artie McFerrin Department of Chemical Engineering at Texas A&M University, conducted live imaging on cells as part of his research. The live imagining shows how the Bone Morphogenetic Protein (BMP) pathway, which cells use to make and transcribe genes, can change with time.
The BMP pathway is a cell signaling pathway that drives cellular decision-making across different tissues. Mistakes in cellular decisions can lead to birth defects and disease states, including cancer.
Reeves and his team are interested in embryonic cells and the effect that the BMP pathway has on deciding what type of cell to become. Their work will help researchers have greater control over stem cells, which would make stem cell therapies cheaper and more reliable.
In their research, which was published in Biology Open, Reeves and his team observed that, after the BMP cellular signal is lost, cells still remember the BMP signal they experienced 20 minutes before.
Eventually we want to control the way these stem cells work. Stem cells would be just one example, but this approach could apply to any cells, like telling them what to do and monitoring their response.
“Our findings suggest that the BMP pathway activates memory in the cells,” Reeves said. “We measured the transcriptional response of a BMP target gene and found the gene remains active, even after the BMP signal that initiated it is lost. As a therapeutic it holds a lot of promise, especially as we understand more about how these cells operate, and we can, with the right chemicals and protocols, basically differentiate cells into whatever we want.”
The Reeves lab showed that because of this signal refinement some cells are exposed to BMP signaling for only a short time. The BMP pathway begins as a broad and weak signal on the dorsal half of the embryo, then 20-30 min later refines into a narrow, intense peak centered on the dorsal midline.
“It's not unheard of for there to be cellular memory, but it isn't the normal case," Reeves said. "It's usually assumed that if a cell is receiving a signal, once that signal is turned off, the cell won't remember it."
Reeves eventually wants to make fine-tuned mid-course corrections on these cells if they begin to differentiate in ways that are not therapeutically useful.
“We can't do things like control gene expression ourselves very well now,” Reeves said. “What we could do with controlled gene expression is look at a bunch of stem cells, monitor what they're doing, and do mid-course corrections if they're not doing exactly what we want them to do.”
By having a deeper level of understanding between the relationship between stimulation and cellular response, it would greatly increase the reliability, reproducibility, and efficiency of controlling gene expression.
“Eventually we want to control the way these stem cells work,” Reeves said. “Stem cells would be just one example, but this approach could apply to any cells, like telling them what to do and monitoring their response.”
Funding for this research is administered by the Texas A&M Engineering Experiment Station (TEES), the official research agency for Texas A&M Engineering.