Journal
DIFFERENTIATION
Volume 125, Issue -, Pages 9-17Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.diff.2022.03.001
Keywords
CREG; Embryonic stem cells; Smooth muscle cells; Contraction; TGF-beta
Categories
Funding
- National Natural Science Foundation of China [81130072]
- Youth Breeding Project for Medical Sci-entific Research Program of PLA [16QNP057]
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The cellular repressor of E1A-stimulated genes (CREG) promotes the differentiation and maturation of embryonic stem cells (ESCs) into vascular smooth muscle cells (SMCs) through the transforming growth factor-beta-smad2/3 pathway.
Vascular smooth muscle cell (SMCs) differentiation is critical for cardiovascular development, but the mechanisms remain largely unknown. The overall aim of this study was to investigate the functional impact and mechanism of cellular repressor of E1A-stimulated genes (CREG) in SMC differentiation. Two embryonic stem cell (ESC) models were generated (1) the overexpression of CREG (CREG-OE), by transfection with PcregIRECS2-EGFP vector, and (2) the knockout of CREG, by transfection with CREG shRNA (CREG-KO). Interesting, SMC-marker levels (SM alpha-actin, SM22, Calponin, and SM-MHC) dramatically increased in CREG-OE ESCs into the SMC while significantly decreased in CREG-KO ESCs during differentiation. After 14 days, and calcium ion concentrations in angiotensin II-stimulated embryoid bodies were increased in CREG-OE ESCs but reduced in CREG-KO ESCs. Consistently, the contractile capacity of SMC from CREG-OE ESC was increased, while the contractile capacity of SMC CREG1 from CREG-KO ESCs was significantly reduced. Furthermore, we demonstrated that CREG promotes differentiation of ESCs to SMCs and maturation of their function through the transforming growth factor-beta-smad2/3 pathway.
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