High levels of Id1 expression define B1 type adult neural stem cells

Cell Stem Cell. 2009 Nov 6;5(5):515-26. doi: 10.1016/j.stem.2009.08.017.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Stem Cells / metabolism*
  • Adult Stem Cells / pathology
  • Animals
  • Antigens, Differentiation / biosynthesis*
  • Antigens, Differentiation / genetics
  • Astrocytes / metabolism*
  • Astrocytes / pathology
  • Cell Differentiation
  • Cell Lineage
  • Cell Survival
  • Cells, Cultured
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Inhibitor of Differentiation Protein 1 / biosynthesis*
  • Inhibitor of Differentiation Protein 1 / genetics
  • Mice
  • Mice, Inbred C57BL
  • Neurogenesis / genetics

Substances

  • Antigens, Differentiation
  • Idb1 protein, mouse
  • Inhibitor of Differentiation Protein 1