Segregation of lipid raft markers including CD133 in polarized human hematopoietic stem and progenitor cells.
During ontogenesis and the entire adult life hematopoietic stem and progenitor cells have the capability to migrate. In comparison to the process of peripheral leukocyte migration in inflammatory responses, the molecular and cellular mechanisms governing the migration of these cells remain poorly understood. A common feature of migrating cells is that they need to become polarized before they migrate. Here we have investigated the issue of cell polarity of hematopoietic stem/progenitor cells in detail. We found that human CD34(+) hematopoietic cells (1) acquire a polarized cell shape upon cultivation, with the formation of a leading edge at the front pole and a uropod at the rear pole; (2) exhibit an amoeboid movement, which is similar to the one described for migrating peripheral leukocytes; and (3) redistribute several lipid raft markers including cholesterol-binding protein prominin-1 (CD133) in specialized plasma membrane domains. Furthermore, polarization of CD34(+) cells is stimulated by early acting cytokines and requires the activity of phosphoinositol-3-kinase as previously reported for peripheral leukocyte polarization. Together, our data reveal a strong correlation between polarization and migration of peripheral leukocytes and hematopoietic stem/progenitor cells and suggest that they are governed by similar mechanisms.
Giebel
Bernd
B
Institut für Transplantationsdiagnostik and Zelltherapeutika, Heinrich Heine Universität Düsseldorf, Moorenstr 5, Geb 14.80, D-40225 Düsseldorf, Germany. giebel@itz.uni-duesseldorf.de
Corbeil
Denis
D
Beckmann
Julia
J
Höhn
Johannes
J
Freund
Daniel
D
Giesen
Kay
K
Fischer
Johannes
J
Kögler
Gesine
G
Wernet
Peter
P
D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34 / Q000378:metabolism; D015415:Biomarkers; D002465:Cell Movement; D016764:Cell Polarity / Q000502:physiology*; D048429:Cell Size; D002478:Cells, Cultured; D015870:Gene Expression; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism; D008563:Membrane Lipids / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism*; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D015415:Biomarkers; D006023:Glycoproteins; D018960:Hyaluronan Receptors; D008563:Membrane Lipids; C000606023:PROM1 protein, human; D010455:Peptides; D011993:Recombinant Fusion Proteins; D019869:Phosphatidylinositol 3-Kinases