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The role of Smad signaling in hematopoiesis

Oncogene volume 24, pages 5676–5692 (2005)Cite this article

Abstract

The TGF-β family of ligands, including TGF-β, bone morphogenetic protein (BMP) and activin, signal through Smad pathways to regulate the fate of hematopoietic progenitor and stem cells during development and postnatally. BMP regulates hematopoietic stem cell (HSC) specification during development, while TGF-β1, 2 and 3 are not essential for the generation of HSCs. BMP4 can increase proliferation of human hematopoietic progenitors, while TGF-β acts as a negative regulator of hematopoietic progenitor and stem cells in vitro. In contrast, TGF-β signaling deficiency in vivo does not affect proliferation of HSCs and does not affect lineage choice either. Therefore, the outcome of Smad signaling is very context dependent in hematopoiesis and regulation of hematopoietic stem and progenitor cells is more complicated in the bone marrow microenvironment in vivo than is seen in liquid cultures ex vivo. Smad signaling regulates hematopoiesis by crosstalk with other regulatory signals and future research will define in more detail how the various pathways interact and how the knowledge obtained can be used to develop advanced cell therapies.

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Acknowledgements

We would like to thank Ann CM Brun and Ulrika Blank for designing several figures and David Scadden for enthusiastic support. We are indebted to our colleagues, Jennifer Moody, Ulrika Blank, Göran Karlsson and Sofie Singbrant for critical reading of the manuscript and for helpful suggestions. SK is supported by grants from The Swedish Cancer Society, The European Commission (CONSERT), The Swedish Gene Therapy Program, The Swedish Medical Research Council, The Swedish Children Cancer Foundation, A Clinical Research Award from Lund University Hospital, The Joint Program on Stem Cell Research supported by The Juvenile Diabetes Research Foundation and The Swedish Medical Research Council. JL is supported by a fellowship from The European Molecular Biology Organization. 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. Molecular Medicine and Gene Therapy, Institute of Laboratory Medicine and The Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, BMC A12, Lund, 221 84, Sweden

    Jonas Larsson & Stefan Karlsson

  2. Center for Regenerative Medicine and Technology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Jonas Larsson

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  1. Jonas Larsson
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  2. Stefan Karlsson
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Correspondence to Stefan Karlsson.

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Larsson, J., Karlsson, S. The role of Smad signaling in hematopoiesis. Oncogene 24, 5676–5692 (2005). https://doi.org/10.1038/sj.onc.1208920

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