Embryonic mesenchymal cells share the potential for smooth muscle differentiation: myogenesis is controlled by the cell’s shape

Abstract

Undifferentiated embryonic mesenchymal cells are round/cuboidal in shape. During development, visceral myogenesis is shortly preceded by mesenchymal cell elongation. To determine the role of the cell's shape on smooth muscle development, undifferentiated embryonic mesenchymal cells from intestine (abundant visceral muscle), lung (some visceral muscle) or kidney (no visceral muscle) were plated under conditions that maintained cell rounding or promoted elongation. Regardless of their fate in vivo, all the cells differentiated into smooth muscle upon elongation as indicated by the expression of smooth muscle-specific proteins and the development of membrane potentials of −60 mV and voltage-dependent Ca2+ currents, characteristic of excitable cells. Smooth muscle differentiation occurred within 24 hours and was independent of cell proliferation. Regardless of their fate in vivo, all the round cells remained negative for smooth muscle markers, had membrane potentials of −30 mV and showed no voltage-activated current. These cells, however, differentiated into smooth muscle upon elongation. The role of the cell's shape in controlling smooth muscle differentiation was not overcome by treatment with retinoic acid, TGF-beta1, PDGF BB or epithelial-conditioned medium (all modulators of smooth muscle differentiation). These studies suggest that the mesenchymal cell shape plays a main role in visceral myogenesis.

Controlled Growth Factor Delivery and Cyclic Stretch Induces a Smooth Muscle Cell-like Phenotype in Adipose-Derived Stem Cells

“…When comparing stretch vs. no stretch, TGLN expression correlated with cell solidity when bone marrow MSCs were plated onto compacted 2D collagen hydrogels [61]. This collectively suggests that the expression of TGLN is responsive to stretch and associates with changes in cell geometry, consistent with cell elongation that is generally described in SMC myogenic differentiation [40,48,53,57]. Together these studies confirm that stretch modifies MSC morphology and protein expression towards SMC myogenic differentiation.…”

“…Fabrication methods that allow the printing of specific geometries and areas of cell adhesion sites have been informative in understanding how cells regulate differentiation and offer an approach to direct this process [13,54,55]. Controlling cell spreading by altering ligand presentation [56] or limiting elongation [57,58] offers another means of regulating differentiation. In this context, cell shape has proven a valuable parameter in predicting and directing phenotype [59,60] with many groups using it as a qualitative indication of the differentiated state.…”

Simulations demonstrate a simple network to be sufficient to control branch point selection, smooth muscle and vasculature formation during lung branching morphogenesis

“…Laminin and fibronectin are two proteins of the extracellular matrix that form between the epithelial and mesenchymal cells. Evidence suggests that smooth muscle differentiation is triggered by their spreading on this basal membrane (Yang et al, 1998;Yang et al, 1999;Zhang et al, 1999;DeLanghe et al, 2005). To reflect this requirement in our new model, we restricted the formation of smooth muscles to a thin layer of mesenchyme, adjacent to the epithelium.…”

“…A number of other factors have been implicated in the control of smooth muscle formation. Smooth muscle differentiation is triggered by cell progenitor interactions with the basal membrane composed of laminin and fibronectin between the epithelial and mesenchymal cells (Yang et al, 1998;Yang et al, 1999;Zhang et al, 1999;DeLanghe et al, 2005). WNT signaling may impact smooth muscle development through the regulation of fibronectin deposition (DeLanghe et al, 2005); WNT2 has also been shown to regulate the expression of Fgf10, Fgfr1c and 2c and Wnt7b (Goss et al, 2011;Yin et al, 2011).…”

RSV-induced changes in a 3-dimensional organoid model of human fetal lungs

“…This study shows that in a 3D organoid system, which has been previously shown to recapitulate the cytological and transcriptional profile of human fetal lungs during the first trimester of pregnancy, RSV infection occurs in a time- and dose-dependent fashion. Consistent with previous data [ 11 , 12 ], RSV replicated better in the SMA-positive mesoderm and vimentin-positive mesenchyme—i.e., the airway smooth muscle (ASM) progenitors [ 13 ]—than in the ciliated or basal fetal airway epithelium. In contrast, more mature fetal ASM does not support viral replication as efficiently.…”