29Oligodendrocyte precursor cells (OPCs) are responsible for spontaneous remyelination 30 after a demyelinating lesion. They are present in large parts of the mouse and human 31 central nervous system, both during development and in adulthood, yet how their 32 physiological behaviour is modified throughout life remains largely unknown. 33 Moreover, the activity of adult human OPCs is still not fully understood. Significantly, 34 most of the molecules involved in OPC-mediated remyelination are also involved in 35 their development, a phenomenon that may be clinically relevant. In this article, we 36 have systematically analyzed the intrinsic properties of OPCs isolated from the cerebral 37 cortex of neonatal, postnatal and adult mice, as well as those recovered from 38 neurosurgical adult human cerebral cortex tissue. We also analyze the response of these 39 cells to two molecules that have known effects on OPC biology during development and 40 that are overexpressed in individuals with Multiple Sclerosis (MS): FGF2 and anosmin-41 1. By analyzing intact OPCs for the first time with H-1 HR-MAS NMR spectroscopy, 42 we show that these cells behave distinctly and that they have different metabolic 43 patterns in function of their stage of maturity. Moreover, their response to FGF-2 and 44 anosmin-1 differs in relation to their developmental stage and in function of the species. 45 Our data reveal that the behaviour of adult human and mouse OPCs differs in a very 46 dynamic way that should be considered when testing drugs and for the proper design of 47 effective pharmacological and/or cell therapies for MS. 48 KEYWORDS 49 oligodendrocyte, myelin, Multiple Sclerosis, human, remyelination. 50 ABBREVIATIONS 51 CNS: Central nervous system 52 DMEM: Dulbecco's Modified Eagle's Medium 53 ECM: extracellular matrix 54 FBS: Fetal Bovine Serum 55 HRMAS: high-resolution magic angle spinning 56 MS: Multiple Sclerosis 57 OPC: Oligodendrocyte precursor cell 58 59 Oligodendrocyte precursor cells (OPCs) are the sole source of oligodendrocytes, the 60 myelin-forming cells in the central nervous system (CNS), and they are widely 61 distributed throughout both the gray and white matter [1-5]. The vast majority of mature 62 oligodendrocytes are born during postnatal life but in adults, oligodendrocytes can also 63 be generated from OPCs that continue to divide and generate new-myelinating cells 64 during adulthood [5-11]. In the adult brain, OPCs constitute 2-3% of the cells inthe 65 gray matter and 5-8% in the white matter [1]. These cells are maintained as a resident 66 population by self-renewal, representing the main proliferative cell type outside the 67 neurogenic regions of the CNS [1,7,12,13]. However, the adult OPC population is not 68 homogeneous as OPCs cycle less intensely with age, their proliferation rate is higher in 69 the whiter matter than in the grey matter, and their differentiation rate declines 70 progressively in postnatal and adult life [1,5,8-11,14,15]. Although the functions of 71 adult-born oligodendrocyte...