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HSCs escape stiffer niche

Hematopoietic stem cells (HSCs) reside in vascular and endosteal niches where they form numerous contacts with the surrounding cells and the extracellular matrix. Remodelling these contacts is crucial for HSC mobilisation from the niche. In addition to chemical signals, the mechanical properties of the microenvironment are crucial for regulating stem cell differentiation and proliferation, but the way in which such mechanical changes could affect HSC mobilisation has remained unclear. On page 3765, Gerd Klein, Joachim Spatz and colleagues now provide evidence that changes in matrix elasticity in the HSC niche in response to specific signals from the nervous system could influence HSC behaviour. By using an in vitro model of the endosteal niche, they show that osteoblasts – which are the major component of the endosteal niche – flatten and remodel their cytoskeleton in response to stimulation with the adrenergic agonist clenbuterol. These changes are accompanied by an increase in stiffness. Furthermore, the authors demonstrate that an increase in matrix stiffness enhances HSC adhesion and migration in a phosphatidylinositol-3-kinase-dependent manner. These findings lead the researchers to speculate that changes in matrix elasticity in the HSC niche lead to increased HSC adhesion and migration, which, in turn, could mediate their mobilisation from the niche.