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The latent transforming growth factor-beta-binding protein-1 promotes in vitro differentiation of embryonic stem cells into endothelium.
- Source :
-
Molecular biology of the cell [Mol Biol Cell] 2000 Dec; Vol. 11 (12), pp. 4295-308. - Publication Year :
- 2000
-
Abstract
- The latent transforming growth factor-beta-binding protein-1 (LTBP-1) belongs to a family of extracellular glycoproteins that includes three additional isoforms (LTBP-2, -3, and -4) and the matrix proteins fibrillin-1 and -2. Originally described as a TGF-beta-masking protein, LTBP-1 is involved both in the sequestration of latent TGF-beta in the extracellular matrix and the regulation of its activation in the extracellular environment. Whereas the expression of LTBP-1 has been analyzed in normal and malignant cells and rodent and human tissues, little is known about LTBP-1 in embryonic development. To address this question, we used murine embryonic stem (ES) cells to analyze the appearance and role of LTBP-1 during ES cell differentiation. In vitro, ES cells aggregate to form embryoid bodies (EBs), which differentiate into multiple cell lineages. We analyzed LTBP-1 gene expression and LTBP-1 fiber appearance with respect to the emergence and distribution of cell types in differentiating EBs. LTBP-1 expression increased during the first 12 d in culture, appeared to remain constant between d 12 and 24, and declined thereafter. By immunostaining, fibrillar LTBP-1 was observed in those regions of the culture containing endothelial, smooth muscle, and epithelial cells. We found that inclusion of a polyclonal antibody to LTBP-1 during EB differentiation suppressed the expression of the endothelial specific genes ICAM-2 and von Willebrand factor and delayed the organization of differentiated endothelial cells into cord-like structures within the growing EBs. The same effect was observed when cultures were treated with either antibodies to TGF-beta or the latency associated peptide, which neutralize TGF-beta. Conversely, the organization of endothelial cells was enhanced by incubation with TGF-beta 1. These results suggest that during differentiation of ES cells LTBP-1 facilitates endothelial cell organization via a TGF-beta-dependent mechanism.
- Subjects :
- Animals
Antibodies immunology
Biomarkers
Carrier Proteins genetics
Carrier Proteins immunology
Cell Differentiation
Cells, Cultured
Endothelium cytology
Endothelium metabolism
Extracellular Matrix metabolism
Gene Expression
Latent TGF-beta Binding Proteins
Mice
Stem Cells metabolism
Time Factors
Transforming Growth Factor beta immunology
Transforming Growth Factor beta physiology
Carrier Proteins physiology
Endothelium embryology
Intracellular Signaling Peptides and Proteins
Stem Cells cytology
Subjects
Details
- Language :
- English
- ISSN :
- 1059-1524
- Volume :
- 11
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Molecular biology of the cell
- Publication Type :
- Academic Journal
- Accession number :
- 11102524
- Full Text :
- https://doi.org/10.1091/mbc.11.12.4295