The Functions and Mechanisms of TGF-β3 Signalling in Controlling the Fate Determinations of Various Types of Stem...

The fate determinations of stem cells are governed by signalling molecules and pathways, and notably, the TGF-β superfamily members play pivotal roles in mediating these decisions. Significantly, TGF-β3 participates in affecting the development of stem cells and their microenvironment. In this review, we address the functions and regulatory networks of TGF-β3 in the fate decisions of several types of stem cells, including neural stem cells, haematopoietic stem cells, odontogenic stem cells, hair-follicle stem cells, adipose-derived stem cells, and mesenchymal stem cells. Specifically, we discuss the biosynthesis, activation, the roles, and mechanisms of TGF-β in influencing the proliferation, differentiation, and cell death of these stem cells, and we further highlight the perspective in this field. TGF-β signalling in stem cells begins with the activation of either integrin-dependent or integrin-independent pathways by binding to cell surface receptors TbRII and TbRI and co-receptor Betaglycan (TR3). TGF-β acts via both classical Smad signalling pathways and a variety of non-classical pathways. Notably, the biological functions of TGF-β3 depend primarily on specific cell type and the existing conditions of stem cells, reflecting the integration of multiple factors including the concentration, duration of action, interactions with other genes and/or non-coding RNAs. This review provides in-depth analyses of the molecular mechanisms through which TGF-β3 affects the fate decisions of adult stem cells, which lays a basis for identifying potential targets and developing future interventions for treating human diseases.