title: CD140a identifies a population of highly myelinogenic, migration-competent and efficiently engrafting human oligodendrocyte progenitor cells.
abstract: Experimental animals with myelin disorders can be treated by transplanting oligodendrocyte progenitor cells (OPCs) into the affected brain or spinal cord. OPCs have been isolated by their expression of gangliosides recognized by mAb A2B5, but this marker also identifies lineage-restricted astrocytes and immature neurons. To establish a more efficient means of isolating myelinogenic OPCs, we sorted fetal human forebrain cells for CD140a, an epitope of platelet derived growth factor receptor (PDGFR)α, which is differentially expressed by OPCs. CD140a(+) cells were isolated as mitotic bipotential progenitors that initially expressed neither mature neuronal nor astrocytic phenotypic markers, yet could be instructed to either oligodendrocyte or astrocyte fate in vitro. Transplanted CD140a(+) cells were highly migratory and robustly myelinated the hypomyelinated shiverer mouse brain more rapidly and efficiently than did A2B5(+)cells. Microarray analysis of CD140a(+) cells revealed overexpression of the oligodendroglial marker CD9, suggesting that CD9(+)/CD140a(+) cells may constitute an even more highly enriched population of myelinogenic progenitor cells.
authors.affiliation: Department of Neurology, University of Rochester Medical Center, Rochester, New York, USA.
authors.forename: Fraser J
authors.initials: FJ
authors.lastname: Sim
authors.forename: Crystal R
authors.initials: CR
authors.lastname: McClain
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Schanz
authors.forename: Tricia L
authors.initials: TL
authors.lastname: Protack
authors.forename: Martha S
authors.initials: MS
authors.lastname: Windrem
authors.forename: Steven A
authors.initials: SA
authors.lastname: Goldman
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D001369:Axons / Q000378:metabolism; D002465:Cell Movement; D049109:Cell Proliferation; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology; D053686:Fetal Stem Cells / Q000166:cytology / Q000378:metabolism; D005333:Fetus / Q000166:cytology; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D009186:Myelin Sheath / Q000378:metabolism*; D009836:Oligodendroglia / Q000166:cytology* / Q000637:transplantation*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D060245:Tetraspanin 29 / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D060245:Tetraspanin 29; D020796:Receptor, Platelet-Derived Growth Factor alpha