Leong SY, Rao VT, Bin JM, Gris P, Sangaralingam M, Kennedy TE, Antel JP. Heterogeneity of oligodendrocyte progenitor cells in adult human brain. Ann Clin Transl Neurol. 2014;1(4):272-83
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 foetal OPCs and mature oligodendrocytes.
METHODS:We isolated human adult and foetal (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, foetal 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 foetal OPCs. Adult OPCs also express different miRNAs compared to mature oligodendrocytes.
INTERPRETATION: We conclude that phenotypically distinct subsets of OPCs are present in adult human brain and these OPCs show differential miRNA expression compared to foetal OPCs and mature oligodendrocytes. These suggest that remyelination in adult brain may involve multiplepopulations of progenitors within the brain and that OPC differentiation in adulthood may be differentially regulated compared to development.
A lot of the knowledge on how oligodenrocytes develop comes from studying rat cells just after birth, however in animals it was found that adult cells may not be the same as in the young. This study looks at human cells and finds that adult myelinating cells are not same as cells in a foetus. The micro RNA are modulates expression of other molecules. What does this mean?
so remyelination may not be the same as myelination.