title: Lipid raft redistribution and morphological cell polarization are separable processes providing a basis for hematopoietic stem and progenitor cell migration.
abstract: Freshly isolated human hematopoietic stem and progenitor cells (HSPCs) are small and round cells which upon cultivation adopt a polarized morphology and redistribute certain cell surface antigens. To functionally dissect this polarization process, we addressed impacts of protein synthesis, HSPC trafficking, cytoskeleton organization or lipid raft integrity on the establishment and maintenance of the cell polarity of human HSPCs. Effects on the morphology, sub-cellular distribution of lipid raft-associated molecular polarization markers (Flotillin-1, Flotillin-2, ICAM-3) and in vitro migration capabilities of treated cells were studied. We could distinguish two levels of cellular polarization, a molecular and a morphological level. Our data suggest that protein synthesis, lipid raft integrity and enzymatic activities of PI3K and aPKC are required to organize the molecular cell polarity. The morphological cell polarization process, however, also depends on actin polymerization and rho-GTPase activities. In summary, our data qualify HSPC polarization processes as new pharmaceutical target to interfere with migratory and with homing capabilities of HSPCs.
authors.affiliation: Institute for Transfusion Medicine, University Hospital Essen, Virchowstr. 179, 45147 Essen, Germany.
authors.forename: André
authors.initials: A
authors.lastname: Görgens
authors.forename: Julia
authors.initials: J
authors.lastname: Beckmann
authors.forename: Anna-Kristin
authors.initials: AK
authors.lastname: Ludwig
authors.forename: Michael
authors.initials: M
authors.lastname: Möllmann
authors.forename: Jan
authors.initials: J
authors.lastname: Dürig
authors.forename: Peter A
authors.initials: PA
authors.lastname: Horn
authors.forename: Lawrence
authors.initials: L
authors.lastname: Rajendran
authors.forename: Bernd
authors.initials: B
authors.lastname: Giebel
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D016764:Cell Polarity / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D021962:Membrane Microdomains / Q000378:metabolism*; D051379:Mice; D016688:Mice, Inbred NOD; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*
chemical_list: D015815:Cell Adhesion Molecules