High Levels of Id1 Expression Define B1 Type Adult Neural Stem Cells

SummaryDefining the molecular identity of stem cells may be critical for formulating a rational strategy for the therapeutic intervention of stem cell dysfunction. We find that high expression of Id1, a dominant-negative helix-loop-helix transcriptional regulator, identifies a rare population of GFAP+ astrocytes with stem cell attributes among the subventricular astrocytes in the adult brain. The rare, long-lived, and relatively quiescent Id1high astrocytes with morphology characteristic of B1 type astrocytes self-renew and generate migratory neuroblasts that differentiate into olfactory bulb interneurons. Cultured Id1high neural stem cells can self-renew asymmetrically and generate a stem and a differentiated cell expressing progressively lower levels of Id1, revealing an 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. We suggest that high expression of a single transcriptional regulator, Id1, molecularly defines the long-sought-after B1 type adult neural stem cells.