Functional blockade of α5β1 integrin induces scattering and genomic landscape remodeling of hepatic progenitor cells
1 Cytogenomics, CIC bioGUNE-CIBEREHD, Par. Tec. Bizkaia Ed. 801 A, 48160 - Derio, Spain
2 IPATIMUP - Institute of Molecular Pathology and Immunology, University of Porto, Portugal
3 Institute for Basic Sciences and Experimental Medicine, Hospital Italiano, Potosi 4240, 1199 - Buenos Aires, Argentina
4 Unidad de Traducción Clínica - Ingeniería de Tejidos, Austral University, Pte Perón 1500, 1635-Pilar, Argentina
5 Institute of Experimental Pathology, Faculty of Health Sciences, National University of Salta, Bolivia 5010, 4400-Salta, Argentina
BMC Cell Biology 2010, 11:81 doi:10.1186/1471-2121-11-81Published: 19 October 2010
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.
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.
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.