Oligodendrocyte Progenitor Cells (OPCs) from Adult Human Brain Expressed Distinct microRNAs Compared to OPCs in Development (P1.155)

Background: Remyelination in multiple sclerosis has been attributed to oligodendrocyte progenitor cells (OPCs) present in brain parenchyma, but the precise identity of such progenitors and the molecular mechanisms controlling their differentiation are incompletely defined. Objective: This study addressed whether different subsets of OPCs are present in adult human brains and examined their expression of specific miRNAs implicated in OPC differentiation. The expression profile of miRNAs was then compared between adult OPCs and OPCs from developing brains. Method: We characterised OPCs based on O4-, A2B5- and MOG-directed fluorescence activated cell sorting (FACS) using samples of surgically resected tissue from adult and fetal (early to mid-2nd trimester) brains, and examined the expression of specific miRNAs using qRT-PCR. Results: Three subsets of putative OPCs were identified in adult brains: i) A2B5(+), ii) O4low and iii) A2B5(+)O4highMOG(+). In comparison, fetal brains contained i) A2B5(+), ii) O4(+) and iii) A2B5(+)O4(+) progenitors, but no MOG(+) cells. We showed that A2B5(+) as well as O4low late OPCs from adult brains could ensheathed dysmyelinated axons derived from shiverer mice. We found that expression of specific miRNAs in adult OPCs differs from fetal OPCs and that adult OPCs showed low to undetected expression of miRNAs that were highly expressed in O4(+) or A2B5(+)O4(+) fetal OPCs. In addition, our data also supports a temporal regulation of miRNA expression during OPC development. Conclusion: We demonstrated that i) there are phenotypically distinct subsets of OPCs in adult human brains, ii) these adult OPCs express different sets of miRNAs specific for differentiation compared to fetal OPCs. Hence, we propose that OPC differentiation in adulthood may be mechanistically different from OPC differentiation during development. Disclosure: Dr. Leong has nothing to disclose. Dr. Rao has nothing to disclose. Dr. Bin has nothing to disclose. Dr. Gris has nothing to disclose. Dr. Sangaralingam has nothing to disclose. Dr. Kennedy has nothing to disclose. Dr. Antel received personal compensation from BiogenIdec, TEVA, emdSerono, Genzyme, Sanofi Aventis, Novartis Dr. Antel received personal compensation from Multiple Sclerosis Journal for serving as a journal editor. . . . . Dr. Antel received financial support for research activities from Novartis effects of FTY on the immune and nervous systems.