Key transcription factors involved in the differentiation of mesenchymal stem cells: review article

Stem cells are undifferentiated biological cells that can differentiate into more specialized cells and divide (through mitosis) to produce more stem cells (self-renew). In mammals, there are two broad types of stem cells: embryonic stem cells, which are isolated from the inner cell mass of blastocysts, and adult stem cells, which are found in various tissues. Mesenchymal stem cells (MSCs) are multipotent cells that are called as one of the most adult stem cells. Due to their highly proliferative potential and their suitable self-renewal capacity, these cells have provided a powerful and promising source for use in the field of regenerative medicine. Also, mesenchymal stem cells are known for their important properties involving multilineage differentiation potential, trophic factor secretion and localization along various organs and tissues. So that MSCs can differentiate into a variety of cell lineages, including: Osteoblasts (bone cells), chondrocytes (cartilage cells), adipocytes (fat cells), myocytes (muscle cells), hepatocytes (liver cells) and endothelial cells. Efficacy of differentiated MSCs to regenerate cells in the injured tissues requires the ability to maintain the differentiation toward the desired cell fate. Since MSCs represent an attractive source for autologous transplantation, cellular and molecular signaling pathways and micro-environmental changes have been studied in order to understand the role of cytokines, chemokines, and transcription factors on the differentiation of MSCs. The differentiation of MSC into a mesenchymal lineage is genetically manipulated and promoted by specific transcription factors associated with a particular cell lineage. Recent studies have explored the integration of transcription factors, including Runx2, Sox9, PPARγ, MyoD, GATA4, and GATA6 in the differentiation of MSCs. Therefore, the overexpression of a single transcription factor in MSCs may promote trans-differentiation into specific cell lineage, which can be used for treatment of some diseases. In this review, we critically discussed and evaluated the role of transcription factors and related signaling pathways that affect the differentiation of MSCs toward adipocytes, chondrocytes, osteocytes, skeletal muscle cells, cardiomyocytes, and smooth muscle cells.