Cartilage oligomeric matrix protein is a novel notch ligand driving embryonic stem cell differentiation towards the smooth muscle lineage.

08:00 EDT 4th July 2018 | BioPortfolio

Summary of "Cartilage oligomeric matrix protein is a novel notch ligand driving embryonic stem cell differentiation towards the smooth muscle lineage."

Cartilage oligomeric matrix protein (COMP), a protective component of vascular extracellular matrix (ECM), maintains the homeostasis of mature vascular smooth muscle cells (VSMCs). However, whether COMP modulates the differentiation of stem cells towards the smooth muscle lineage is still elusive. Firstly, purified mouse COMP directly induced mouse embryonic stem cell (ESC) differentiation into VSMCs both in vitro and in vivo, while the silencing of endogenous COMP markedly inhibited ESC-VSMC differentiation. RNA-Sequencing revealed that Notch signaling was significantly activated by COMP during ESC-VSMC differentiation, whereas the inhibition of Notch signaling attenuated COMP-directed ESC-VSMC differentiation. Furthermore, COMP deficiency inhibited Notch activation and VSMC differentiation in mice. Through silencing distinct Notch receptors, we identified that Notch1 mainly mediated COMP-initiated ESC-VSMC differentiation. Mechanistically, COMP N-terminus directly interacted with the EGF11-12 domain of Notch1 and activated Notch1 signaling, as evidenced by co-immunoprecipitation and mammalian two-hybrid assay. In conclusion, COMP served as a potential ligand of Notch1, thereby driving ESC-VSMC differentiation.


Journal Details

This article was published in the following journal.

Name: Journal of molecular and cellular cardiology
ISSN: 1095-8584


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Medical and Biotech [MESH] Definitions

PROTEOGLYCANS-associated proteins that are major components of EXTRACELLULAR MATRIX of various tissues including CARTILAGE; and INTERVERTEBRAL DISC structures. They bind COLLAGEN fibers and contain protein domains that enable oligomer formation and interaction with other extracellular matrix proteins such as CARTILAGE OLIGOMERIC MATRIX PROTEIN.

Major component of chondrocyte EXTRACELLULAR MATRIX of various tissues including bone, tendon, ligament, SYNOVIUM and blood vessels. It binds MATRILIN PROTEINS and is associated with development of cartilage and bone.

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A type of CARTILAGE whose matrix contains ELASTIC FIBERS and elastic lamellae, in addition to the normal components of HYALINE CARTILAGE matrix. Elastic cartilage is found in the EXTERNAL EAR; EUSTACHIAN TUBE; EPIGLOTTIS; and LARYNX.

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