Gene expression profiling and analysis of signaling pathways involved in priming and differentiation of human neural stem cells

Neuroscience. 2006;138(1):133-48. doi: 10.1016/j.neuroscience.2005.11.041. Epub 2006 Jan 18.


Human neural stem cells have the ability to differentiate into all three major cell types in the CNS including neurons, astrocytes and oligodendrocytes. The multipotency of human neural stem cells shed a light on the possibility of using stem cells as a therapeutic tool for various neurological disorders including neurodegenerative diseases and neurotrauma that involve a loss of functional neurons. We have discovered previously a priming procedure to direct primarily cultured human neural stem cells to differentiate into almost pure neurons when grafted into adult CNS. However, the molecular mechanism underlying this phenomenon is still unknown. To unravel transcriptional changes of human neural stem cells upon priming, cDNA microarray was used to study temporal changes in human neural stem cell gene expression profile during priming and differentiation. As a result, transcriptional levels of 520 annotated genes were detected changed in at least at two time points during the priming process. In addition, transcription levels of more than 3000 hypothetical protein encoding genes and EST genes were modulated during the priming and differentiation processes of human neural stem cells. We further analyzed the named genes and grouped them into 14 functional categories. Of particular interest, key cell signal transduction pathways, including the G-protein-mediated signaling pathways (heterotrimeric and small monomeric GTPase pathways), the Wnt signaling pathway and the TGF-beta pathway, are modulated by the neural stem cell priming, suggesting important roles of these key signaling pathways in priming and differentiation of human neural stem cells.

Publication types

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

MeSH terms

  • Bone Morphogenetic Proteins / physiology
  • Cell Differentiation / physiology
  • Cells
  • Cyclic AMP / physiology
  • Fluorescent Antibody Technique
  • GTP Phosphohydrolases / metabolism
  • Gene Expression Profiling
  • Humans
  • Lymphotoxin-alpha / physiology
  • Microcomputers
  • Mitogen-Activated Protein Kinases / physiology
  • Multigene Family
  • Neurons / physiology*
  • Oligonucleotide Array Sequence Analysis
  • RNA / biosynthesis
  • RNA / genetics
  • Receptors, G-Protein-Coupled / physiology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / physiology*
  • Stem Cells / physiology*
  • Tretinoin / physiology
  • Type C Phospholipases / physiology
  • Wnt Proteins / physiology


  • Bone Morphogenetic Proteins
  • Lymphotoxin-alpha
  • Receptors, G-Protein-Coupled
  • Wnt Proteins
  • Tretinoin
  • RNA
  • Cyclic AMP
  • Mitogen-Activated Protein Kinases
  • Type C Phospholipases
  • GTP Phosphohydrolases