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


CONCLUSIONS
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.
Cytogenomics, CIC bioGUNE-CIBEREHD, Par, Tec, Bizkaia Ed, 801 A, 48160 - Derio, Spain.
Luciano
L
Vellón
Félix
F
Royo
Rune
R
Matthiesen
José
J
Torres-Fuenzalida
Alicia
A
Lorenti
Luis A
LA
Parada
D000818:Animals; D000906:Antibodies / Q000276:immunology; D002448:Cell Adhesion; D002465:Cell Movement; D042002:Chromatin Assembly and Disassembly / Q000502:physiology; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D016678:Genome; D022781:Hepatocytes / Q000166:cytology*; D039081:Integrin alpha5beta1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000906:Antibodies; D039081:Integrin alpha5beta1; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases