TGF-β signaling in the control of hematopoietic stem cells

Blood is a tissue with high cellular turnover, and its production is a tightly orchestrated process that requires constant replenishment. All mature blood cells are generated from hematopoietic stem cells (HSCs), which are the self-renewing units that sustain lifelong hematopoiesis. HSC behavior, such as self-renewal and quiescence, is regulated by a wide array of factors, including external signaling cues present in the bone marrow. The transforming growth factor-beta (TGF-beta) family of cytokines constitutes a multifunctional signaling circuitry, which regulates pivotal functions related to cell fate and behavior in virtually all tissuesof thebody. In the hematopoietic system, TGF-beta signaling controls a wide spectrum of biological processes, from homeostasis of the immune system to quiescence and self-renewal of HSCs. Here, we review key features and emerging concepts pertaining to TGF-beta and downstream signaling pathways in normal HSC biology, featuring aspects of aging, hematologic disease, and how this circuitry may be exploited for clinical purposes in the future.