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 stiffness, α-SMA, YAP, and MSC differentiation. Consistent with in vitro findings, nuclear localization of YAP was positively correlated in α-SMA expressing stromal cells of adiposarcoma and osteosarcoma. We propose that α-SMA mediated contraction plays a critical role in mechanically regulating MSC fate by controlling YAP/TAZ activation.

journal_name

Stem Cell Reports

journal_title

Stem cell reports

authors

Talele NP,Fradette J,Davies JE,Kapus A,Hinz B

doi

10.1016/j.stemcr.2015.05.004

subject

Has Abstract

pub_date

2015-06-09 00:00:00

pages

1016-30

issue

6

issn

2213-6711

pii

S2213-6711(15)00133-2

journal_volume

4

pub_type

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