Different roles of TGF-β in the multi-lineage differentiation of stem cells

Abstract

Stem cells are a population of cells that has infinite or long-term self-renewal ability and can produce various kinds of descendent cells. Transforming growth factor β (TGF-β) family is a superfamily of growth factors, including TGF-β1, TGF-β2 and TGF-β3, bone morphogenetic proteins, activin/inhibin, and some other cytokines such as nodal, which plays very important roles in regulating a wide variety of biological processes, such as cell growth, differentiation, cell death. TGF-β, a pleiotropic cytokine, has been proved to be differentially involved in the regulation of multi-lineage differentiation of stem cells, through the Smad pathway, non-Smad pathways including mitogen-activated protein kinase pathways, phosphatidylinositol-3-kinase/AKT pathways and Rholike GTPase signaling pathways, and their cross-talks. For instance, it is generally known that TGF-β promotes the differentiation of stem cells into smooth muscle cells, immature cardiomyocytes, chondrocytes, neurocytes, hepatic stellate cells, Th17 cells, and dendritic cells. However, TGF-β inhibits the differentiation of stem cells into myotubes, adipocytes, endothelial cells, and natural killer cells. Additionally, TGF-β can provide competence for early stages of osteoblastic differentiation, but at late stages TGF-β acts as an inhibitor. The three mammalian isoforms (TGF-β1, 2 and 3) have distinct but overlapping effects on hematopoiesis. Understanding the mechanisms underlying the regulatory effect of TGF-β in the stem cell multi-lineage differentiation is of importance in stem cell biology, and will facilitate both basic research and clinical applications of stem cells. In this article, we discuss the current status and progress in our understanding of different mechanisms by which TGF-β controls multi-lineage differentiation of stem cells.

Human Embryonic Stem Cells Prevent T-Cell Activation by Suppressing Dendritic Cells Function via TGF-Beta Signaling Pathway

“…Searching for a soluble factor responsible for inhibition of lymphocyte activation, we decided to test whether hESCs express TGF‐beta, one of the most prominent anti‐inflammatory cytokines . It is well documented that TGF‐beta signaling is responsible for maintaining the pluripotent state of hESCs . Indeed, hESCs express TGF‐beta as was demonstrated by flow cytometry (Fig.…”

Avoidance of total knee arthroplasty in early osteoarthritis of the knee with intra-articular implantation of autologous activated peripheral blood stem cells versus hyaluronic acid: A randomized controlled trial with differential effects of growth factor addition

“…Another possible role for CD105 on MSCs may be in mediating TGF beta signaling during chondrogenic differentiation. All TGF beta isoforms [44] are capable of inducing MSCs from human and other species along the chondrogenic pathway. Moreover, TGF beta in PRP works along with FGF2 to assist in the migration of stromal cells to the site of injury [45].…”

Effect of the IkBα mutant gene delivery to mesenchymal stem cells on rat chronic pancreatitis

“…TGF-β l is a multifunctional cytokine that combines with its receptors, RI and RII, at the cell surface to form complexes and regulate cell growth and differentiation (Wang et al, 2012). TGF-β l complexes play important roles in tissue fibrosis and repair by stimulating cell matrix synthesis and inhibiting degradation.…”