Cell biological study of the RANDAM-2 high positive cells and RANDAM-2 low/negative cells in mouse central nervous system.

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RANDAM-2, a type-I transmembrane antigen constitutively expressed on the excitatory neuronal cell lineage during mouse neurogenesis, shows the highest expression level between embryonic day 8.5 (E8.5) and E10.5. As the period well overlaps with the proliferating stages of neural stem cells (NSCs), it is conceivable that RANDAM-2 is involved in the proliferation and/or the resulting neural differentiation. In this paper, we show that NSCs and NPCs can be isolated as RANDAM-2^<high+> and RANDAM-2^<low+/-> cells, respectively, by positive selection with a monoclonal antibody specific to RANDAM-2. The isolated RANDAM-2^<high+> cells had the characteristics as the highly self-renewal capability and potential for multilineage differentiation into neural cells. In contrast, almost all of the RANDAM-2^<low+/-> cells exhibited not only the extremely low self-renewability but the differentiation capability restricted to neurons. These two cell populations also differed from each other in terms of the expression level of molecules associated with neural differentiation. These findings demonstrate that RANDAM-2 can be regarded as a useful marker for isolation of the NSCs, and suggest that its high expression takes part in the retention of the neural cells within the innate properties as NSCs.