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

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A road map towards defining the role of Smad signaling in hematopoietic stem cells. / Utsugisawa, Taiju; Moody, Jennifer; Aspling, Marie; Nilsson, Eva C; Carlsson, Leif; Karlsson, Stefan.

In: Stem Cells, Vol. 24, No. 4, 2006, p. 1128-1136.

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Utsugisawa, T, Moody, J, Aspling, M, Nilsson, EC, Carlsson, L & Karlsson, S 2006, 'A road map towards defining the role of Smad signaling in hematopoietic stem cells.', Stem Cells, vol. 24, no. 4, pp. 1128-1136. https://doi.org/10.1634/stemcells.2005-0263

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Utsugisawa, Taiju ; Moody, Jennifer ; Aspling, Marie ; Nilsson, Eva C ; Carlsson, Leif ; Karlsson, Stefan. / A road map towards defining the role of Smad signaling in hematopoietic stem cells. In: Stem Cells. 2006 ; Vol. 24, No. 4. pp. 1128-1136.

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TY - JOUR

T1 - A road map towards defining the role of Smad signaling in hematopoietic stem cells.

AU - Utsugisawa, Taiju

AU - Moody, Jennifer

AU - Aspling, Marie

AU - Nilsson, Eva C

AU - Carlsson, Leif

AU - Karlsson, Stefan

PY - 2006

Y1 - 2006

N2 - 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.

AB - 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.

KW - activin

KW - bone morphogenic proteins

KW - factor-beta

KW - Smad signaling

KW - hematopoietic stem cells

KW - transforming growth

U2 - 10.1634/stemcells.2005-0263

DO - 10.1634/stemcells.2005-0263

M3 - Article

C2 - 16357343

VL - 24

SP - 1128

EP - 1136

JO - Stem Cells

JF - Stem Cells

SN - 1549-4918

IS - 4

ER -