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

Moldrich, R. X.
Dauphinot, Luce
Laffaire, Julien
Vitalis, Tania
Beart, P. M.
Rossier, Jean
Vivien, Denis
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Published in Journal of neuroscience research. 2009, vol. 87, no. 14, p. 3143-3152
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 AnimalsCell Differentiation/geneticsCell ProliferationCells, CulturedDisease Models, AnimalDown SyndromeGene Expression/ physiologyGene Expression ProfilingGenotypeImmunohistochemistryMaleMiceMicrospheresNeocortex/physiopathologyNeuroglia/pathology/physiologyNeurons/ pathology/ physiologyOligonucleotide Array Sequence AnalysisReverse Transcriptase Polymerase Chain ReactionStem Cells/ pathology/physiology
PMID: 19472221
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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 https://archive-ouverte.unige.ch/unige:8907

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Deposited on : 2010-07-12

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