Neural precursor cells derived from human embryonic brain retain regional specificity

J Neurosci Res. 2004 Mar 15;75(6):817-24. doi: 10.1002/jnr.20046.


Recent studies have revealed that neural precursor cells can be expanded not only from the subventricular zone and hippocampus but also from other regions of the human embryonic brain. To determine the regional differences of these precursor cells, we divided the brain of a 9-week-old human embryo into four parts, i.e., telencephalon, diencephalon, mesencephalon, and rhombencephalon. All cultures of the tissues yielded neurospheres, and these spheres gave rise to neurons, astrocytes, and oligodendrocytes. An analysis of clonal populations revealed that these precursor cells were multipotent, and two region-specific differences in neural precursor cells were revealed: 1) The precursor cells from the rostral part of the brain tended to proliferate faster than those from the caudal part, and 2) the precursor cells from the diencephalon and mesencephalon gave rise to more tyrosine hydoxylase (TH)-positive neurons than those from the telencephalon and rhombencephalon. When 50-day-cultured spheres were caused to differentiate, the percentage of TH-positive cells per total cell population was 1.2% for diencephalic and mesencephalic precursors, whereas it was 0.4% for telencephalic and rhombencephalic ones. Furthermore, the TH-positive cells from diencephalic and mesencephalic precursors were large, multipolar, and gamma-aminobutyric acid (GABA)-negative, which suggested that these cells were midbrain dopaminergic neurons. In contrast, TH-positive cells from telencephalic and rhombencephalic precursors were small, bipolar, and GABA-positive. These results suggest that human neural precursor cells might have the potential to differentiate into a variety of cells but retain regional specificity.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Southern / methods
  • Brain / embryology*
  • Brain / enzymology
  • Brain / metabolism
  • Cell Count / methods
  • Cell Differentiation / physiology*
  • Cells, Cultured
  • Embryo, Mammalian / cytology*
  • Fluorescent Antibody Technique / methods
  • Galactosylceramidase / metabolism
  • Gene Expression
  • Glial Fibrillary Acidic Protein / metabolism
  • Green Fluorescent Proteins
  • Hedgehog Proteins
  • Humans
  • Luminescent Proteins / metabolism
  • Mice
  • Microtubule-Associated Proteins / metabolism
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neurons / metabolism*
  • RNA, Messenger / biosynthesis
  • RNA-Binding Proteins / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Stem Cells / metabolism*
  • Time Factors
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transfection / methods
  • Tubulin / metabolism
  • Tyrosine 3-Monooxygenase / metabolism*
  • gamma-Aminobutyric Acid / metabolism


  • Glial Fibrillary Acidic Protein
  • Hedgehog Proteins
  • Luminescent Proteins
  • MSI1 protein, human
  • Microtubule-Associated Proteins
  • Msi1h protein, mouse
  • Nerve Tissue Proteins
  • RNA, Messenger
  • RNA-Binding Proteins
  • Trans-Activators
  • Tubulin
  • beta3 tubulin, mouse
  • Green Fluorescent Proteins
  • gamma-Aminobutyric Acid
  • Tyrosine 3-Monooxygenase
  • Galactosylceramidase