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Bipotential oligodendrocyte-type-2 astrocyte (0-2A) progenitor cells, which give rise to oligodendrocytes and type-2 astrocytes in cultures of rat optic nerve, are one of the few cell types in which most aspects of proliferation and differentiation can be manipulated in a defmed in vitro environment. Previous studies have shown that 0-2A progenitors exposed to platelet-derived growth factor (PDGF) divide as migratory bipolar cells a limited number of times, with a cell cycle time of 18 hr, before clonally related progenitors differentiate into nondividing oligodendrocytes with a timing similar to that seen in vivo. In contrast, 0-2A progenitors grown in the absence of mitogen do not divide but instead differentiate prematurely into oligodendrocytes, and progenitors exposed to appropriate inducing factors differentiate into type-2 astrocytes. We now have found that 0-2A progenitors can be induced to undergo continuous self-renewal in the absence of oligodendrocytic differentiation by exposure to a combination of PDGF and basic fibroblast growth factor (bFGF). With the exception of the inhibition of differentiation, the 0-2A progenitors exposed to PDGF and bFGF behaved similarly to those exposed to PDGF alone. In contrast, progenitors exposed to basic bFGF alone were multipolar, had a cell-cycle length of 45 hr, showed little migratory behavior, underwent premature oligodendrocytic differentiation, and did not cease division upon expression of oligodendrocyte marker antigens. Thus, inhibition of differentiation required the presence of both mitogens. Our results demonstrate that PDGF and bFGF act on 0-2A progenitors as both inducers of division and as regulators of differentiation that modulate multiple aspects of 0-2A progenitor development and, additionally, reveal a previously unrecognized means of regulating self-renewal processes, wherein cooperation between growth factors promotes continuous division in the absence of differentiation.To better understand the cellular and molecular interactions that regulate the development of multipotential precursor cells, we have been studying the control of division and differentiation in oligodendrocyte-type-2 astrocyte (O-2A) progenitor cells of the rat optic nerve (1). These glial precursors represent one of the few cell types in which most aspects of differentiation and proliferation can be manipulated in a defined in vitro environment. For example, 0-2A progenitors grown in chemically defined medium in the absence of mitogen do not divide but instead differentiate rapidly into oligodendrocytes (1-3), while progenitors exposed to appropriate inducing factors differentiate into type-2 astrocytes (1, 4, 5).Several studies have demonstrated that the induction of cell division in 0-2A progenitors is associated with the expression of several characteristics that are quite distinct from the events of mitosis (see Fig. 1 for a summary). 0-2A progenitors induced to divide by platelet-derived growth factor (PDGF) or by growth in the presence of type-1 astrocytes (wh...

Abstract. We have been studying the differing characteristics of oligodendrocyte-type-2 astrocyte (O-2A) progenitors isolated from optic nerves of perinatal and adult rats. These two cell types display striking differences in their in vitro phenotypes . In addition, the O-2Aari-al progenitor population appears to have a limited lifespan in vivo, while 0-2Aadull progenitors appear to be maintained throughout life. O-2Aari-1 progenitors seem to have largely disappeared from the optic nerve by 1 mo after birth, and are not detectable in cultures derived from optic nerves of adult rats. In contrast, O-2A°ß'1 progenitors can first be isolated from optic nerves of 7-d-old rats and are still present in optic nerves of 1-yr-old rats. These observations raise two questions : (a) From what source do 0-2Aadull progenitors originate ; and (b) how is the O-2A°°d, progenitor

Distinguishing aquaporin-4 IgG(AQP4-IgG)-negative neuromyelitis optica spectrum disorders (NMOSD) from opticospinal predominant multiple sclerosis (MS) is a clinical challenge with important treatment implications. The objective of the study was to examine whether expert clinicians diagnose and treat NMO/MS overlapping patients in a similar way. 12 AQP4-IgG-negative patients were selected to cover the range of clinical scenarios encountered in an NMO clinic. 27 NMO and MS experts reviewed their clinical vignettes, including relevant imaging and laboratory tests. Diagnoses were categorized into four groups (NMO, MS, indeterminate, other) and management into three groups (MS drugs, immunosuppression, no treatment). The mean proportion of agreement for the diagnosis was low (po = 0.51) and ranged from 0.25 to 0.73 for individual patients. The majority opinion was divided between NMOSD versus: MS (nine cases), monophasic longitudinally extensive transverse myelitis (LETM) (1), acute disseminated encephalomyelitis (ADEM) (1) and recurrent isolated optic neuritis (RION) (1). Typical NMO features (e.g., LETM) influenced the diagnosis more than features more consistent with MS (e.g., short TM). Agreement on the treatment of patients was higher (po = 0.64) than that on the diagnosis with immunosuppression being the most common choice not only in patients with the diagnosis of NMO (98 %) but also in those indeterminate between NMO and MS (74 %). The diagnosis in AQP4-IgG-negative NMO/MS overlap syndromes is challenging and diverse. The classification of such patients currently requires new diagnostic categories, which incorporate lesser degrees of diagnostic confidence. Long-term follow-up may identify early features or biomarkers, which can more accurately distinguish the underlying disorder.