Molecular identity of neural stem cells: High levels of Id1 expression defines the B1 type adult neural stem cells

Understanding the molecular identity of stem cells may be critical for formulating a rational strategy for the therapeutic intervention of stem cell dysfunction. I find that high expression of Id1, a dominant-negative helix-loop-helix transcriptional regulator, defines a rare population of subventricular GFAP+ astrocytes in the adult brain. Some Mash1-expressing transit amplifying cells express lower levels of Id1, suggesting a gradient of Id1 levels among the subventricular Id1-expressing cells. The rare, long-lived, and relatively quiescent GFAP+ Id1high astrocytes with morphology characteristic of B1 type astrocytes self-renew and generate migratory neuroblasts that differentiate into olfactory bulb interneurons. Cultured Id1high subventricular neural stem cells can self-renew asymmetrically and generate a stem and a differentiated cell expressing progressively lower levels of Id1, revealing the Id1 gradient in unperturbed cells of subventricular neurogenic lineages. Moreover, Id genes are necessary to confer self-renewal capacity, a characteristic of stem cell identity. Finally, hippocampal subgranular GFAP+Id1 high astrocytes also give rise to neurons. Thus, I suggest that the high Id1 expression molecularly defines the long-sought-after GFAP+ B1 type adult neural stem cells.