Smooth Myocytes - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 408

The regulation of YAP and TAZ mediators requires RhoA GTPase and actin-myosin
contractility. Transmitter YAP precludes expression of the contractile phenotype of
smooth myocytes, as it impedes activity of the myocardin-SRF complex.

8.5.3.2 Differentiation of Vascular Smooth Myocytes

Chromatin remodeling enables SMC differentiation, in particular demethylation of
dimethylated Lys9 of histone-3 (H3K 9 me 2 ) and Lys20 of histone-4 (H4K 20 me 2 )
that allows decompaction of SMC marker gene chromatin in SMC precursors [ 748 ].
Differentiated vascular smooth myocytes possess several specific histone tail modi-
fications (acetylation [H3K 9 ac, H3K 14 ac, and H4ac) and methylation (H3K 4 me 2 ,
H3K 79 me 2 ) at SMC marker gene CC(A/T-rich)6GG (CArG) boxes. These his-
tone modifications enable access of the myocardin-SRF complex and coactivator
P300 histone acetyltransferase to SMC-specific CArGs, thereby activating gene
transcription. Dedifferentiation of vascular smooth myocytes (phenotype change)
results from removal of these histone modifications from chromatin at SMC marker
gene CArG boxes, except H3K 4 me 2 that may help maintain SMC marker genes as
euchromatin and permit redifferentiation under adequate conditions [ 748 ].
During embryo- and fetogenesis, vascular smooth myocytes have various sources
(e.g., neural crest, somites, and proepicardium, in particular mesoangioblasts of
the dorsal aorta in mammals, in addition to endothelial cells upon endothelial-
mesenchymal differentiation), according to the vascular compartment, in addition
to a common population of progenitor cells, such as TIE1

,PECAM1 low , Cdh5

+ − ,

PTPRc precursors [ 751 ]. These precursors also express smA and homeodomain-

containing factor Msx2.
Notch and Wnt control vSMC differentiation and modulate their phenotype
according to exerted stimuli via transcription factors and cofactors that determine
gene expression program.
Notch signaling in TIE1

−

precursor cells is involved in developing arteries,
whatever the vascular compartment, but not in mature vascular smooth myocytes,
i.e.,

+

once the artery is stabilized. Notch upregulates transcription of the

mesenchymal markers smA and PDGFR β ; it supports endothelial-mesenchymal

transdifferentiation.

8.5.3.3 Notch Signaling in vSMC Specification

Smooth myocytes of major arteries arise from several cell lineages. Smooth
myocytes of the developing arch artery, ductus arteriosus, and proximal regions of
the major aortic arch branches derive from the cardiac neural crest; those of the
root of the aorta and pulmonary artery from the second heart field; those of the the
descending aorta from somites [ 752 ].