Removing a Regulatory Protein Eliminates the Link Between Stem Cell Differentiation and Matrix Rigidity

They reported in June 5, 2012, online edition of the journal Science Signaling that multipotent cells derived from native cardiac tissue continually monitored the rigidity of the extracellular matrix upon which the cells were growing and showed enhanced proliferation, endothelial differentiation, and morphogenesis when the cell substratum rigidity closely matched that of myocardium.

Mechanical regulation of these diverse processes required p190RhoGAP, a guanosine triphosphatase–activating protein for RhoA (Ras homolog gene family, member A - a small GTPase protein known to regulate the actin cytoskeleton in the formation of stress fibers) acting through RhoA-dependent and -independent mechanisms. Natural or induced decreases in the abundance of p190RhoGAP triggered a series of developmental events by coupling cell-cell and cell-substratum interactions to genetic circuits controlling differentiation.

"It was the kind of master regulator of this process," said senior author Dr. Andre Levchenko, professor of biomedical engineering at Johns Hopkins University. "And an even bigger surprise was that if we directly forced this molecule to disappear, we no longer needed the special heart-matched surfaces. When the master regulator was missing, the stem cells started to form blood vessels, even on glass. In biology, finding a central regulator like this is like finding a pot of gold."

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