Scientific article
English

Proliferation deficits and gene expression dysregulation in Down's syndrome (Ts1Cje) neural progenitor cells cultured from neurospheres

Published inJournal of neuroscience research, vol. 87, no. 14, p. 3143-3152
Publication date2009
Abstract

Down's syndrome neurophenotypes are characterized by mental retardation and a decreased brain volume. To identify whether deficits in proliferation could be responsible for this phenotype, neural progenitor cells were isolated from the developing E14 neocortex of Down's syndrome partial trisomy Ts1Cje mice and euploid (WT) littermates and grown as neurospheres. Ts1Cje neural progenitors proliferated at a slower rate, because of a longer cell cycle, and a greater number of cells were positive for glial fibrillary acidic protein. An increase in cell death was also noted. Gene expression profiles of neural progenitor cells from Ts1Cje and WT showed that 54% of triploid genes had expression ratios (Ts1Cje/WT) significantly greater than the expected diploid gene ratio of 1.0. Some diploid genes associated with proliferation, differentiation, and glial function were dysregulated. Interestingly, proliferation and gene expression dysregulation detected in the Ts1Cje mice did not require overexpression of the chromosome 21 genes amyloid precursor protein (App) and soluble superoxide dismutase 1 (Sod1).

Keywords
  • Animals
  • Cell Differentiation/genetics
  • Cell Proliferation
  • Cells, Cultured
  • Disease Models, Animal
  • Down Syndrome
  • Gene Expression/ physiology
  • Gene Expression Profiling
  • Genotype
  • Immunohistochemistry
  • Male
  • Mice
  • Microspheres
  • Neocortex/physiopathology
  • Neuroglia/pathology/physiology
  • Neurons/ pathology/ physiology
  • Oligonucleotide Array Sequence Analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stem Cells/ pathology/physiology
Citation (ISO format)
MOLDRICH, R. X. et al. Proliferation deficits and gene expression dysregulation in Down’s syndrome (Ts1Cje) neural progenitor cells cultured from neurospheres. In: Journal of neuroscience research, 2009, vol. 87, n° 14, p. 3143–3152. doi: 10.1002/jnr.22131
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Journal ISSN0360-4012
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