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TGF-β signaling in the control of hematopoietic stem cells

Ulrika Blank and Stefan Karlsson

Abstract

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 life-long hematopoiesis. HSC behavior, such as self-renewal and quiescence, are regulated by a wide array of factors, including external signaling cues present in the bone marrow. The Transforming Growth Factor-β (TGF-β) family of cytokines constitutes a multifunctional signaling circuitry, which regulates pivotal functions related to cell fate and behavior in virtually all tissues of the body. In the hematopoietic system, TGF-β 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-β and downstream signaling pathways in normal HSC biology, featuring aspects of aging, hematological disease, and how this circuitry may be exploited for clinical purposes in the future.

  • Submitted December 19, 2014.
  • Accepted March 30, 2015.