Neuronal differentiation of mouse embryonic stem cells: lineage selection and forced differentiation paradigms.
Primitive embryonic stem cells are an ideal starting cell population for studies of gene expression and lineage segregation during development. Despite their potential, it has been difficult to determine culture conditions that cause single-lineage differentiation of these pluripotent cells. Both genetic and epigenetic approaches have been taken to promote neuronal differentiation of embryonic stem cells, including aggregation, exposure to the nonspecific teratogen/morphogen retinoic acid, low-density culture, exposure to growth/differentiation factors, and forced differentiation following expression of lineage-restricted "developmental control" genes. In the current investigation, a hybrid approach involving genetic techniques of "lineage selection" or "forced differentiation" has been employed to develop primitive neural progenitor cell lines. These lines form an important starting point to examine the cascades of gene expression (and inhibition) during neuronal and glial lineage segregation, to study growth factor effects on neural differentiation, and ultimately to provide a source of cells for transplantation to a damaged nervous system.
O'Shea
K S
KS
Department of Cell and Developmental Biology, 4748 MSII Building, University of Michigan Medical School, Ann Arbor, MI 48109-0616, USA. oshea@umich.edu
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D019070:Cell Lineage / Q000187:drug effects; D004622:Embryo, Mammalian / Q000166:cytology*; D005822:Genetic Vectors / Q000235:genetics / Q000494:pharmacology; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000494:pharmacology; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000494:pharmacology; D064231:Nestin; D009474:Neurons / Q000166:cytology*; D012641:Selection, Genetic; D013234:Stem Cells / Q000166:cytology*; D014162:Transfection
D051792:Basic Helix-Loop-Helix Proteins; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; D064231:Nestin; C577485:Nes protein, mouse; C093564:Neurogenic differentiation factor 1