Chromobox protein homolog 3 is essential for stem cell differentiation to smooth muscles in vitro and in embryonic arteriogenesis
Autor: | Shu Ye, Andriani Margariti, Gang Wang, Zhenling Luo, Xiaoke Yin, Qingzhong Xiao, Lingfang Zeng, Qingbo Xu, Manuel Mayr |
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Rok vydání: | 2011 |
Předmět: |
medicine.medical_specialty
Serum Response Factor Chromosomal Proteins Non-Histone Cellular differentiation Cell Myocytes Smooth Muscle Active Transport Cell Nucleus Formins Neovascularization Physiologic Chick Embryo Biology Chromodomain Avian Proteins Mice Viral Proteins Internal medicine Serum response factor medicine Myocyte Animals Protein Interaction Domains and Motifs Amino Acid Sequence Promoter Regions Genetic Cells Cultured Embryonic Stem Cells Neural crest Cell Differentiation Embryonic stem cell Cell biology medicine.anatomical_structure Endocrinology Branchial Region Neural Crest Gene Knockdown Techniques cardiovascular system Stem cell Cardiology and Cardiovascular Medicine Carrier Proteins |
Zdroj: | Arteriosclerosis, thrombosis, and vascular biology. 31(8) |
ISSN: | 1524-4636 |
Popis: | Objective— Smooth muscle cell (SMC) differentiation is a critical process during cardiovascular formation and development, but the underlying molecular mechanism remains unclear. Methods and Results— Here we demonstrated that chromobox protein homolog 3 (Cbx3) is crucial for SMC differentiation from stem cells and that the chromodomain and chromoshadow domain of Cbx3 are responsible for Cbx3-induced SMC differentiation. Moreover, we identified that 4 amino acids (165 to 168) within the chromoshadow domain of Cbx3 are key elements for Cbx3 interaction with Dia-1- and Cbx3-induced SMC differentiation. Mechanistically, we found that Cbx3 mediates SMC differentiation through modulating serum response factor (SRF) recruitment to the promoters of SMC genes, in which the interaction between Cbx3 and Dia-1/SRF plays a crucial role in this process. Moreover, our in vivo study demonstrated that the misexpression of Cbx3 within neural crest cells of chick embryos resulted in the death of chick embryos at early stages because of the maldevelopment of branchial arch arteries. Conclusion— Our findings suggest that the interaction between Cbx3 and Dia-1/SRF is essential for SMC differentiation from stem cells and for the development of functional cardiovascular system. |
Databáze: | OpenAIRE |
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