GSE60642
Active repression of Sox9 by Jag1 is required for silencing the default chondrogenic fate of the vascular smooth muscle wall [set 2]
Acquisition and maintenance of vascular smooth muscle fate is essential for the morphogenesis and function of the circulatory system. Loss of contractile properties or changes in the identity of vascular smooth muscle cells (vSMC) can result in structural alterations associated with aneurysms and vascular wall calcifications. Here we report that maturation of sclerotome-derived vSMC is dependent on a transcriptional switch between mouse embryonic days 13 and 14.5. At this time point, Jag1-mediated repression of sclerotome transcription factors Pax1, scleraxis and Sox9 is necessary to fully enable vSMC maturation. Specifically, Notch signaling in vSMC antagonizes sclerotome and cartilage transcription factors, and promotes upregulation of contractile genes. In the absence of Jag1, vSMC acquire a chondrocytic transcriptional repertoire that can lead to ossification of the vascular wall. Importantly, our findings suggest that sustained Notch signaling is essential throughout vSMC life to maintain contractile function, prevent vSMC reprogramming and promote vascular wall integrity. Overall design: mRNA profile of vSMC from the descending aorta of  14.5 embryos Wild type (WT), SMC Jag1-heterozygous (HTZ) and SMC Jag1-null (KO) was generated by  deep sequencing, in duplicate.