High levels of Id1 expression define B1 type adult neural stem cells.
Defining 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 Id1(high) astrocytes with morphology characteristic of B1 type astrocytes self-renew and generate migratory neuroblasts that differentiate into olfactory bulb interneurons. Cultured Id1(high) 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.
Nam
Hyung-song
HS
Sloan-Kettering Memorial Cancer Center, Sloan-Kettering Institute, New York, NY 10065, USA. hyn2001@med.cornell.edu
Benezra
Robert
R
D053687:Adult Stem Cells / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis* / Q000235:genetics; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D019070:Cell Lineage; D002470:Cell Survival; D002478:Cells, Cultured; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D051798:Inhibitor of Differentiation Protein 1 / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D055495:Neurogenesis / Q000235:genetics
D000943:Antigens, Differentiation; C497455:Idb1 protein, mouse; D051798:Inhibitor of Differentiation Protein 1