A road map towards defining the role of Smad signaling in hematopoietic stem cells.
(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:
https://lup.lub.lu.se/record/148660
- author
- Utsugisawa, Taiju LU ; Moody, Jennifer LU ; Aspling, Marie LU ; Nilsson, Eva C LU ; Carlsson, Leif and Karlsson, Stefan LU
- organization
- publishing date
- 2006
- 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
- Oxford University 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
- 2023-01-05 03:09:57
@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}}, keywords = {{activin; bone morphogenic proteins; factor-beta; Smad signaling; hematopoietic stem cells; transforming growth}}, language = {{eng}}, number = {{4}}, pages = {{1128--1136}}, publisher = {{Oxford University 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}}, }