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A road map towards defining the role of Smad signaling in hematopoietic stem cells.

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Author

  • Taiju Utsugisawa
  • Jennifer Moody
  • Marie Aspling
  • Eva C Nilsson
  • Leif Carlsson
  • Stefan Karlsson

Summary, in English

The transforming growth factor-beta (TGF-beta) superfamily encompasses the ligands and receptors for TGF-beta, bone morphogenic proteins (BMPs), and Activins. Cellular response to ligand is context-dependent and may be controlled by specificity and/or redundancy of expression of these superfamily members. Several pathways within this family have been implicated in the proliferation, differentiation, and renewal of hematopoictic stem cells (HSCs); however, their roles and redundancies at the molecular level are poorly understood in the rare HSC. Here we have characterized the expression of TGF-beta superfamily ligands, receptors, and Smads in murine HSCs and in the Lhx2-hematopoietic progenitor cell (Lhx2-HPC) line. We demonstrate a remarkable likeness between these two cell types with regard to expression of the majority of receptors and Smads necessary for the transduction of signals from TGF-beta, BMP, and Activin. We have also evaluated the response of these two cell types to various ligands in proliferation assays. In this regard, primary cells and the Lhx2-HPC line behave similarly, revealing a suppressive effect of Activin-A that is similar to that of TGF-beta in bulk cultures and no effect of BMP-4 on proliferation. Signaling studies that verify the phosphorylation of Smad2 (Activin and TGF-beta) and Smad1/5 (BMP) confirm cytosolic responses to these ligands. In addition to providing a thorough characterization of TGF-beta superfamily expression in HSCs, our results define the Lhx2-HPC line as an appropriate model for molecular characterization of Smad signaling.

Publishing year

2006

Language

English

Pages

1128-1136

Publication/Series

Stem Cells

Volume

24

Issue

4

Document type

Journal article

Publisher

AlphaMed Press

Topic

  • Cell and Molecular Biology

Keywords

  • activin
  • bone morphogenic proteins
  • factor-beta
  • Smad signaling
  • hematopoietic stem cells
  • transforming growth

Status

Published

ISBN/ISSN/Other

  • ISSN: 1549-4918