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Functional blockade of α5β1 integrin induces scattering and genomic landscape remodeling of hepatic progenitor cells.

Vellón L, Royo F, Matthiesen R, Torres-Fuenzalida J, Lorenti A, Parada LA - BMC Cell Biol. (2010)

Bottom Line: Cell scattering is a physiological process executed by stem and progenitor cells during embryonic liver development and postnatal organ regeneration.These responses were accompanied by conspicuous spatial reorganization of centromeres, while integrin genes conserved their spatial positioning in the interphase nucleus.Collectively, our results demonstrate that α5β1 integrin functional blockade induces cell migration of hepatic progenitor cells, and that this involves a dramatic remodeling of the nuclear landscape.

View Article: PubMed Central - HTML - PubMed

Affiliation: Cytogenomics, CIC bioGUNE-CIBEREHD, Par, Tec, Bizkaia Ed, 801 A, 48160 - Derio, Spain.

ABSTRACT

Background: Cell scattering is a physiological process executed by stem and progenitor cells during embryonic liver development and postnatal organ regeneration. Here, we investigated the genomic events occurring during this process induced by functional blockade of α5β1 integrin in liver progenitor cells.

Results: Cells treated with a specific antibody against α5β1 integrin exhibited cell spreading and scattering, over-expression of liver stem/progenitor cell markers and activation of the ERK1/2 and p38 MAPKs signaling cascades, in a similar manner to the process triggered by HGF/SF1 stimulation. Gene expression profiling revealed marked transcriptional changes of genes involved in cell adhesion and migration, as well as genes encoding chromatin remodeling factors. These responses were accompanied by conspicuous spatial reorganization of centromeres, while integrin genes conserved their spatial positioning in the interphase nucleus.

Conclusion: Collectively, our results demonstrate that α5β1 integrin functional blockade induces cell migration of hepatic progenitor cells, and that this involves a dramatic remodeling of the nuclear landscape.

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Related in: MedlinePlus

Radial position of integrin genes during migration of MLP29 cells. Three-dimensional FISH analysis was performed with BAC clones for the Itgb1 or Itgb3 loci and the position of fluorescent signals was determined using computational programs for image analysis. Left panels, 3D reconstruction of MLP29 cell nuclei subjected to FISH analysis with a probe for the Itgb1 and Itgb3 genes. Right panel, absolute radial position of these genes in control and treated cells. Scale bar = 3 μm.
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Figure 8: Radial position of integrin genes during migration of MLP29 cells. Three-dimensional FISH analysis was performed with BAC clones for the Itgb1 or Itgb3 loci and the position of fluorescent signals was determined using computational programs for image analysis. Left panels, 3D reconstruction of MLP29 cell nuclei subjected to FISH analysis with a probe for the Itgb1 and Itgb3 genes. Right panel, absolute radial position of these genes in control and treated cells. Scale bar = 3 μm.

Mentions: Taking into account that α5β1 functional blockade and HGF/SF1 stimulation resulted in up-regulation of the genes encoding the integrin β1 and β3 sub-units; we asked whether these genes undergo repositioning. To this end, we analyzed the nuclear radial position of each gene independently by interphase 3D DNA-FISH and the results from 50-70 nuclei per experiment were plotted on cumulative distribution graphs. The preferential radial position of Itgb1 and Itgb3 was between 80% and 100% of the relative radius in control cells. Pair-wise comparisons by Kolmogorov-Smirnov statistical tests, demonstrated that these genes did not change their position upon α5β1 functional blockade or HGF/SF1 stimulation (p > 0, 05) (Figures 8A and 8B). Considering the increase in the expression of β1 and β3 integrins associated with cell scattering, these results suggest that the Itgb1 or Itgb3 radial positions do not depend on gene activity.


Functional blockade of α5β1 integrin induces scattering and genomic landscape remodeling of hepatic progenitor cells.

Vellón L, Royo F, Matthiesen R, Torres-Fuenzalida J, Lorenti A, Parada LA - BMC Cell Biol. (2010)

Radial position of integrin genes during migration of MLP29 cells. Three-dimensional FISH analysis was performed with BAC clones for the Itgb1 or Itgb3 loci and the position of fluorescent signals was determined using computational programs for image analysis. Left panels, 3D reconstruction of MLP29 cell nuclei subjected to FISH analysis with a probe for the Itgb1 and Itgb3 genes. Right panel, absolute radial position of these genes in control and treated cells. Scale bar = 3 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2967514&req=5

Figure 8: Radial position of integrin genes during migration of MLP29 cells. Three-dimensional FISH analysis was performed with BAC clones for the Itgb1 or Itgb3 loci and the position of fluorescent signals was determined using computational programs for image analysis. Left panels, 3D reconstruction of MLP29 cell nuclei subjected to FISH analysis with a probe for the Itgb1 and Itgb3 genes. Right panel, absolute radial position of these genes in control and treated cells. Scale bar = 3 μm.
Mentions: Taking into account that α5β1 functional blockade and HGF/SF1 stimulation resulted in up-regulation of the genes encoding the integrin β1 and β3 sub-units; we asked whether these genes undergo repositioning. To this end, we analyzed the nuclear radial position of each gene independently by interphase 3D DNA-FISH and the results from 50-70 nuclei per experiment were plotted on cumulative distribution graphs. The preferential radial position of Itgb1 and Itgb3 was between 80% and 100% of the relative radius in control cells. Pair-wise comparisons by Kolmogorov-Smirnov statistical tests, demonstrated that these genes did not change their position upon α5β1 functional blockade or HGF/SF1 stimulation (p > 0, 05) (Figures 8A and 8B). Considering the increase in the expression of β1 and β3 integrins associated with cell scattering, these results suggest that the Itgb1 or Itgb3 radial positions do not depend on gene activity.

Bottom Line: Cell scattering is a physiological process executed by stem and progenitor cells during embryonic liver development and postnatal organ regeneration.These responses were accompanied by conspicuous spatial reorganization of centromeres, while integrin genes conserved their spatial positioning in the interphase nucleus.Collectively, our results demonstrate that α5β1 integrin functional blockade induces cell migration of hepatic progenitor cells, and that this involves a dramatic remodeling of the nuclear landscape.

View Article: PubMed Central - HTML - PubMed

Affiliation: Cytogenomics, CIC bioGUNE-CIBEREHD, Par, Tec, Bizkaia Ed, 801 A, 48160 - Derio, Spain.

ABSTRACT

Background: Cell scattering is a physiological process executed by stem and progenitor cells during embryonic liver development and postnatal organ regeneration. Here, we investigated the genomic events occurring during this process induced by functional blockade of α5β1 integrin in liver progenitor cells.

Results: Cells treated with a specific antibody against α5β1 integrin exhibited cell spreading and scattering, over-expression of liver stem/progenitor cell markers and activation of the ERK1/2 and p38 MAPKs signaling cascades, in a similar manner to the process triggered by HGF/SF1 stimulation. Gene expression profiling revealed marked transcriptional changes of genes involved in cell adhesion and migration, as well as genes encoding chromatin remodeling factors. These responses were accompanied by conspicuous spatial reorganization of centromeres, while integrin genes conserved their spatial positioning in the interphase nucleus.

Conclusion: Collectively, our results demonstrate that α5β1 integrin functional blockade induces cell migration of hepatic progenitor cells, and that this involves a dramatic remodeling of the nuclear landscape.

Show MeSH
Related in: MedlinePlus