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

Utsugisawa, Taiju LU ; Moody, Jennifer LU ; Aspling, Marie LU ; Nilsson, Eva C LU ; Carlsson, Leif and Karlsson, Stefan LU orcid (2006) In Stem Cells 24(4). p.1128-1136
Abstract
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
activin, bone morphogenic proteins, factor-beta, Smad signaling, hematopoietic stem cells, transforming growth
in
Stem Cells
volume
24
issue
4
pages
1128 - 1136
publisher
AlphaMed Press
external identifiers
  • wos:000240636300036
  • pmid:16357343
  • scopus:33745511278
  • pmid:16357343
ISSN
1549-4918
DOI
10.1634/stemcells.2005-0263
language
English
LU publication?
yes
id
affe323a-e3a0-49ac-947f-804442d0891d (old id 148660)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16357343&dopt=Abstract
date added to LUP
2016-04-01 16:51:39
date last changed
2021-08-18 02:56:32
@article{affe323a-e3a0-49ac-947f-804442d0891d,
  abstract     = {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.},
  author       = {Utsugisawa, Taiju and Moody, Jennifer and Aspling, Marie and Nilsson, Eva C and Carlsson, Leif and Karlsson, Stefan},
  issn         = {1549-4918},
  language     = {eng},
  number       = {4},
  pages        = {1128--1136},
  publisher    = {AlphaMed Press},
  series       = {Stem Cells},
  title        = {A road map towards defining the role of Smad signaling in hematopoietic stem cells.},
  url          = {http://dx.doi.org/10.1634/stemcells.2005-0263},
  doi          = {10.1634/stemcells.2005-0263},
  volume       = {24},
  year         = {2006},
}