Abstract
Neural precursor cells (NPCs) are self-renewing, multipotent progenitors that give rise to neurons, astrocytes and oligodendrocytes in the central nervous system (CNS). Fetal NPCs have attracted attention for their potential use in studying normal CNS development. Several studies of rodent neural progenitors have suggested that chemokines and their receptors are involved in directing NPC migration during CNS development. In this study, we established a consistent system to culture human NPCs and examined the expression of chemokine receptors on these cells. NPCs were found to express the markers nestin and CD133 and to differentiate into neurons, astrocytes and oligodendrocytes at the clonal level. Flow cytometry and RNase protection assay (RPA) indicated that NPCs express high levels of CXCR4 and low levels of several other chemokine receptors. When examined using a chemotaxis assay, NPCs were able to respond to CXCL12/SDF-1alpha, a ligand of CXCR4. Treatment with anti-CXCR4 antibody or HIV-1 gp120 abolished the migratory response of NPCs towards CXCL12/SDF-1alpha. These findings suggest that CXCR4 may play a significant role in directing NPC migration during CNS development.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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AC133 Antigen
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Antigens, CD / metabolism
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Astrocytes / cytology
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Astrocytes / drug effects
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Astrocytes / metabolism
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Biomarkers
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Cell Differentiation / drug effects
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Cell Differentiation / physiology
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Cell Lineage / physiology
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Cell Movement / drug effects
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Cell Movement / physiology
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Cells, Cultured
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Chemokine CXCL12
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Chemokines / metabolism*
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Chemokines, CXC / metabolism
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Chemokines, CXC / pharmacology
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Glycoproteins / metabolism
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HIV Envelope Protein gp120 / metabolism
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HIV Envelope Protein gp120 / pharmacology
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Humans
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Intermediate Filament Proteins / metabolism
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Nerve Tissue Proteins / metabolism
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Nestin
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Neurons / cytology
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Neurons / drug effects
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Neurons / metabolism*
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Oligodendroglia / cytology
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Oligodendroglia / drug effects
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Oligodendroglia / metabolism
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Peptides / metabolism
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Receptors, CXCR4 / metabolism*
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Stem Cells / cytology
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Stem Cells / drug effects
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Stem Cells / metabolism*
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Telencephalon / cytology
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Telencephalon / embryology*
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Telencephalon / metabolism*
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Up-Regulation / drug effects
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Up-Regulation / physiology
Substances
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AC133 Antigen
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Antigens, CD
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Biomarkers
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CXCL12 protein, human
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Chemokine CXCL12
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Chemokines
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Chemokines, CXC
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Glycoproteins
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HIV Envelope Protein gp120
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Intermediate Filament Proteins
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NES protein, human
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Nerve Tissue Proteins
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Nestin
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PROM1 protein, human
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Peptides
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Receptors, CXCR4