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Updated: Sep 28, 2025

Differentiation of Atrial Cardiomyocytes from Pluripotent Stem Cells Using the BMP Antagonist Grem2
Published on: March 10, 2016
CREG ameliorates embryonic stem cell differentiation into smooth muscle cells by modulation of TGF-β expression
Chengfei Peng1, Xiaoping Shao2, Xiaoxiang Tian1
1Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, Liaoning, China.
Abstract:
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 Pcreg-IRECS2-EGFP vector, and (2) the knockout of CREG, by transfection with CREG shRNA (CREG-KO). Interesting, SMC-marker levels (SM α-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-β -smad2/3 pathway.
Insights
Cellular repressor of E1A-stimulated genes (CREG) promotes vascular smooth muscle cell (SMC) differentiation and function. CREG enhances SMC marker expression and contractile capacity via the transforming growth factor-β -smad2/3 pathway.
Area of Science:
- Cardiovascular Biology
- Stem Cell Differentiation
- Molecular Mechanisms
Background:
- Vascular smooth muscle cell (SMC) differentiation is crucial for cardiovascular development.
- The precise molecular mechanisms governing SMC differentiation are not fully understood.
Purpose of the Study:
- To investigate the role and mechanism of cellular repressor of E1A-stimulated genes (CREG) in SMC differentiation.
- To determine CREG's impact on SMC function and maturation.
Main Methods:
- Generated embryonic stem cell (ESC) models with CREG overexpression (CREG-OE) and CREG knockout (CREG-KO).
- Assessed SMC marker expression (e.g., SM α-actin, SM22, Calponin, SM-MHC) during differentiation.
- Measured calcium ion concentrations and contractile capacity in differentiated SMCs.
Main Results:
- CREG-OE ESCs showed significantly increased SMC marker levels and contractile capacity.
- CREG-KO ESCs exhibited decreased SMC marker expression and reduced contractile function.
- CREG-OE enhanced calcium ion concentrations in stimulated embryoid bodies, while CREG-KO reduced them.
Conclusions:
- CREG plays a vital role in promoting ESC differentiation into functional SMCs.
- CREG enhances SMC maturation and contractile function.
- The transforming growth factor-β -smad2/3 pathway mediates CREG's effects on SMC differentiation and function.
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