title: Proliferation deficits and gene expression dysregulation in Down's syndrome (Ts1Cje) neural progenitor cells cultured from neurospheres.
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).
authors.affiliation: Laboratoire de Neurobiologie et Diversité Cellulaire, CNRS UMR7637, ESPCI, Paris, France.
authors.forename: Randal X
authors.initials: RX
authors.lastname: Moldrich
authors.forename: Luce
authors.initials: L
authors.lastname: Dauphinot
authors.forename: Julien
authors.initials: J
authors.lastname: Laffaire
authors.forename: Tania
authors.initials: T
authors.lastname: Vitalis
authors.forename: Yann
authors.initials: Y
authors.lastname: Hérault
authors.forename: Philip M
authors.initials: PM
authors.lastname: Beart
authors.forename: Jean
authors.initials: J
authors.lastname: Rossier
authors.forename: Denis
authors.initials: D
authors.lastname: Vivien
authors.forename: Corinne
authors.initials: C
authors.lastname: Gehrig
authors.forename: Stylianos E
authors.initials: SE
authors.lastname: Antonarakis
authors.forename: Robert
authors.initials: R
authors.lastname: Lyle
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Potier
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004314:Down Syndrome; D015870:Gene Expression / Q000502:physiology*; D020869:Gene Expression Profiling; D005838:Genotype; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008863:Microspheres; D019579:Neocortex / Q000503:physiopathology; D009457:Neuroglia / Q000473:pathology / Q000502:physiology; D009474:Neurons / Q000473:pathology* / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000473:pathology* / Q000502:physiology