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The role of Smad signaling in hematopoiesis and translational hematology

Leukemia volume 25, pages 1379–1388 (2011)Cite this article

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Abstract

Hematopoietic stem cells (HSCs) reside in the bone marrow (BM) of adult individuals and function to produce and regenerate the entire blood and immune system over the course of an individual's lifetime. Historically, HSCs are among the most thoroughly characterized tissue-specific stem cells. Despite this, the regulation of fate options, such as self-renewal and differentiation, has remained elusive, partly because of the expansive plethora of factors and signaling cues that govern HSC behavior in vivo. In the BM, HSCs are housed in specialized niches that dovetail the behavior of HSCs with the need of the organism. The Smad-signaling pathway, which operates downstream of the transforming growth factor-β (TGF-β) superfamily of ligands, regulates a diverse set of biological processes, including proliferation, differentiation and apoptosis, in many different organ systems. Much of the function of Smad signaling in hematopoiesis has remained nebulous due to early embryonic lethality of most knockout mouse models. However, recently new data have been uncovered, suggesting that the Smad-signaling circuitry is intimately linked to HSC regulation. In this review, we bring the Smad-signaling pathway into focus, chronicling key concepts and recent advances with respect to TGF-β-superfamily signaling in normal and leukemic hematopoiesis.

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Acknowledgements

This work was supported by the European Commission (Stemexpand); Swedish Medical Research Council; Swedish Cancer Society; Swedish Children Cancer Foundation; Clinical Research Award from Lund University Hospital and a grant from The Tobias Foundation awarded by the Royal Academy of Sciences. (SK). The Lund Stem Cell Center is supported by a Center of Excellence grant in life sciences from the Swedish Foundation for Strategic Research.

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  1. Division of Molecular Medicine and Gene Therapy, Laboratory Medicine, Lund Stem Cell Center, Lund University Hospital, Lund, Sweden

    U Blank & S Karlsson

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Blank, U., Karlsson, S. The role of Smad signaling in hematopoiesis and translational hematology. Leukemia 25, 1379–1388 (2011). https://doi.org/10.1038/leu.2011.95

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