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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