Table 1 The functional mechanisms of transcription factors and microRNAs in the cardiac development and direct reprogramming
From: Direct reprogramming of fibroblasts into cardiomyocytes
Factors | Direct reprogramming (crude, artificial transcription factor dosage) | Cardiac development (fine balance of transcription factor expression) |
|---|---|---|
GATA4, MEF2C, TBX5 [15] | GATA4, MEF2C, and TBX5 are the core components of direct reprogramming | NKX2.5, Mesp1, and Myocd: expressed in cardiac progenitor cells (CPCs), and induce the development of cell fate to the mesoblastema layer GATA4, HAND2, and TBX5: induce the cardiac gene expression |
TBX5 [25] | Promotes the differentiation of transfected cells into beating cardiomyocytes | |
NKX2.5 | Induces Ryr2 gene expression | |
Hand2 | Induces tropomyosin and cTnT in human dermal fibroblasts | |
Mesp1 [26] | Expressed in CPCs and programs nascent mesoderm toward a cardiovascular cell fate | |
Myocd | Regulates the development of cardiomyocytes and smooth muscle cells, and increased the expression of cardiac sarcomeric proteins | |
miR-1, miR-133, miR-208, miR-499 [24] | Alters H3K27 methyltransferase and demethylase expression | Promotes cardiomyocyte proliferation and suppresses apoptosis; increases expression of contractile proteins (MHC); influences the development of ventricular septum |
miR-1 [27] | Promotes cardiomyocyte proliferation and suppresses apoptosis | Promotes cardiomyocyte proliferation and suppresses apoptosis |
miR-133 [28] | miR-133-mediated Snai1 repression | Promotes cardiomyocyte proliferation |