Genes aren't the sole driver instructing cells to build multicellular structures, tissues, and organs.
Keck School of Medicine of USCNov 20 2024 Gene s aren't the sole driver instructing cells to build multicellular structures, tissues, and organs. In a new paper published in Nature Communications, USC Stem Cell scientist Leonardo Morsut and Caltech computational biologist Matt Thomson characterize the influence of another important developmental driver: cell density, or how loosely or tightly cells are packed into a given space.
The study used two types of mouse cells-;connective tissue cells and stem cells-;engineered to carry a synthetic cellular communication system or "genetic circuit." This circuit is based on something Morsut developed called "synNotch," which is a protein that scientists genetically engineer into a cell to serve as a "sensor.
"We would see different outcomes of the patterning when we would start with genetically identical cells in different numbers," said Morsut. "So that was puzzling at the beginning. I remember Marco came in and told me once that the experiment worked, but only in half of the plate. And when we looked at it more carefully, we started seeing that there was a gradient of cell density that seemed to correlate with differences in patterning.
"For me, this was one of the first times in my life where computational modeling has been able to predict behaviors that look like what actually happens in the cells," said Thomson, who is an assistant professor of computational biology at Caltech and an investigator with the Heritage Medical Research Institute. "Here, it helped guide us to think about how the cell density, proliferation rate, signaling, and all these different things conspire.
It's okay be a little dense To understand how cell density was exerting these effects, co-first author Josquin Courte, a postdoc in the Morsut Lab, conducted a series of experiments that yielded a surprising discovery. Greater cell density induces stress that leads to a quicker breakdown of not only synNotch in particular, but also cell surface sensors in general.
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