Open AccessHeterogeneity of oligodendrocyte progenitor cells in adult human brain
Author(s) -
Leong Soo Yuen,
Rao Vijayaraghava T. S.,
Bin Jenea M.,
Gris Pavel,
Sangaralingam Mugundhine,
Kennedy Timothy E.,
Antel Jack P.
Publication year - 2014
Publication title -
annals of clinical and translational neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.824
H-Index - 42
ISSN - 2328-9503
DOI - 10.1002/acn3.55
Subject(s) - remyelination , progenitor cell , oligodendrocyte , neuroscience , olig2 , multiple sclerosis , biology , microrna , fetus , progenitor , stem cell , myelin , medicine , immunology , microbiology and biotechnology , central nervous system , gene , pregnancy , genetics
Objective Remyelination in multiple sclerosis has been attributed to the presence of oligodendrocyte progenitor cells ( OPC s) in brain parenchyma. However, the precise identity of these progenitors is poorly defined. Here, we characterized populations of OPC s in the adult human brain and examined their myelination capacity and profile of mi RNA s. Comparisons were made with fetal OPC s 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 q RT ‐ PCR to analyze expression of selective miRNAs implicated in OPC biology. Results Three subsets of putative OPC s 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 OPC s, adult OPC s have the capacity to ensheathe cerebellar axons. However, adult OPC s exhibit low to undetectable expression of mi RNA s that were highly expressed in O4‐expressing fetal OPC s. Adult OPC s also express different mi RNA s compared to mature oligodendrocytes. Interpretation We conclude that phenotypically distinct subsets of OPC s are present in adult human brain and these OPC s show differential mi RNA expression compared to fetal OPC s 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.