TGF-β signaling and its role in the regulation of hematopoietic stem cells.

Transforming growth factor-betas (TGF-βs) and their family members that include bone morphogenic proteins and activins have been implicated in the regulation of proliferation, hibernation, quiescence and differentiation of hematopoietic stem cells (HSCs). Increasing evidence suggests that the superfamily of TGF-βs play an integral role in the intercellular cross-talk between the stem cells and their microenvironment as well as within the cells at an intracellular level. Active sites of hematopoiesis, such as fetal liver and bone marrow are known to have abundant presence of TGF-β indicating their importance in the maintenance and regulation of hematopoiesis. One of the striking features of TGF-β superfamily is the variety of effects they evoke, contingent on the developing history of the responding cells. In the present review, we discuss the Smad-dependent and Smad-independent TGF-β signaling pathways in order to understand and underscore their role in the regulation of HSCs.