title: Heterogeneity of oligodendrocyte progenitor cells in adult human brain.
abstract: OBJECTIVE
  Remyelination in multiple sclerosis has been attributed to the presence of oligodendrocyte progenitor cells (OPCs) in brain parenchyma. However, the precise identity of these progenitors is poorly defined. Here, we characterized populations of OPCs in the adult human brain and examined their myelination capacity and profile of miRNAs. Comparisons were made with fetal OPCs and mature oligodendrocytes.
  
  
  METHODS
  We isolated human adult and fetal (early-to-mid second trimester) OPCs from surgically resected brain tissues using O4-, A2B5-, and MOG-directed fluorescence activated cell sorting and transplanted them into dysmyelinated shiverer slices to examine their myelination capacity. We used qRT-PCR to analyze expression of selective miRNAs implicated in OPC biology.
  
  
  RESULTS
  Three subsets of putative OPCs were identified in adult brains: (1) A2B5(+), (2) O4(low), and (3) A2B5(+)O4(high)MOG(+) progenitors. In comparison, fetal brains contained (1) A2B5(+), (2) O4(+), and (3) A2B5(+)O4(+) progenitors, but no MOG(+) cells. We demonstrate that like fetal OPCs, adult OPCs have the capacity to ensheathe cerebellar axons. However, adult OPCs exhibit low to undetectable expression of miRNAs that were highly expressed in O4-expressing fetal OPCs. Adult OPCs also express different miRNAs compared to mature oligodendrocytes.
  
  
  CONCLUSIONS
  We conclude that phenotypically distinct subsets of OPCs are present in adult human brain and these OPCs show differential miRNA expression compared to fetal OPCs and mature oligodendrocytes. These suggest that remyelination in adult brain may involve multiple populations of progenitors within the brain and that OPC differentiation in adulthood may be differentially regulated compared to development.
authors.affiliation: Neuroimmunology Unit, Montreal Neurological Institute, McGill University Montreal, Quebec, Canada, H3A 2B4.
authors.forename: Soo Yuen
authors.initials: SY
authors.lastname: Leong
authors.affiliation: Neuroimmunology Unit, Montreal Neurological Institute, McGill University Montreal, Quebec, Canada, H3A 2B4.
authors.forename: Vijayaraghava T S
authors.initials: VT
authors.lastname: Rao
authors.affiliation: Center for Neuronal Survival, Montreal Neurological Institute, McGill University Montreal, Quebec, Canada, H3A 2B4.
authors.forename: Jenea M
authors.initials: JM
authors.lastname: Bin
authors.affiliation: Center for Neuronal Survival, Montreal Neurological Institute, McGill University Montreal, Quebec, Canada, H3A 2B4.
authors.forename: Pavel
authors.initials: P
authors.lastname: Gris
authors.affiliation: Institute of Parasitology, McGill University Montreal, Quebec, Canada, H9X 3V9.
authors.forename: Mugundhine
authors.initials: M
authors.lastname: Sangaralingam
authors.affiliation: Center for Neuronal Survival, Montreal Neurological Institute, McGill University Montreal, Quebec, Canada, H3A 2B4.
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Kennedy
authors.affiliation: Neuroimmunology Unit, Montreal Neurological Institute, McGill University Montreal, Quebec, Canada, H3A 2B4.
authors.forename: Jack P
authors.initials: JP
authors.lastname: Antel