Expression of α-Smooth Muscle Actin Determines the Fate of Mesenchymal Stromal Cells.

ABSTRACT: Pro-fibrotic microenvironments of scars and tumors characterized by increased stiffness stimulate mesenchymal stromal cells (MSCs) to express α-smooth muscle actin (α-SMA). We investigated whether incorporation of α-SMA into contractile stress fibers regulates human MSC fate. Sorted α-SMA-positive MSCs exhibited high contractile activity, low clonogenicity, and differentiation potential limited to osteogenesis. Knockdown of α-SMA was sufficient to restore clonogenicity and adipogenesis in MSCs. Conversely, α-SMA overexpression induced YAP translocation to the nucleus and reduced the high clonogenicity and adipogenic potential of α-SMA-negative MSCs. Inhibition of YAP rescued the decreased adipogenic differentiation potential induced by α-SMA, establishing a mechanistic link between matrix

SUBMITTER: Talele NP 

PROVIDER: S-EPMC4471834 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature