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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Apr 30, 2009 |
| Title |
Delayed cell cycling in DS Ts1Cje neural precursor cells results in gene expression dysregulation |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Down syndrome neurophenotypes are characterized by mental retardation and a decreased brain volume. In order to identify whether deficits in proliferation, differentiation or survival could be responsible for this phenotype, neural precursor cells (NPCs) were isolated from the developing E14 neocortex of Down syndrome partial trisomy Ts1Cje mice and euploid (WT) littermates. Proliferation, cell differentiation and cell death assays revealed that Ts1Cje NPCs proliferated at a slower rate, due to a longer cell cycle and that a greater number of cells were positive for glial fibrillary acidic protein. An increase in Ts1Cje NPC cell death was also noted. Gene expression profiling was conducted on RNA extracted from Ts1Cje and WT NPCs. Approximately 54% of triploid gene expression ratios were significantly greater than the expected diploid gene ratio of 1.0. A number of diploid genes associated with differentiation, glial function and proliferation were dysregulated. The evidence points to a delay in cellular cycling that could exert stress on the NPC population, which might result in cellular death and a mobilization of glial cell survival responses. Importantly, these phenotypic changes, which mimic those seen in Down syndrome individuals, do not require over-expression of amyloid precursor protein (App) or soluble superoxide dismutase 1 (Sod1). In conclusion, early developmental proliferation deficits in Down syndrome result in secondary morphological changes that can impact on cognitive development and function.
Keywords: Down syndrome, Neocortical precursor cells, transcriptome, proliferation
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| Overall design |
Neural precursor cells (NPCs) were isolated from mouse E14 neocortex of Down syndrome Ts1Cje mice and euploid littermates. We compared gene expression profiles from trisomic and wild-type cells using pangenomic microarrays.
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| Contributor(s) |
Moldrich R, Dauphinot L, Laffaire J, Vitalis T, Hérault Y, Beart P, Rossier J, Antonarakis S, Gehrig C, Lyle R, Potier M |
| Citation(s) |
19472221 |
| Submission date |
Dec 06, 2007 |
| Last update date |
Mar 17, 2012 |
| Contact name |
Luce Dauphinot |
| E-mail(s) |
luce.dauphinot@upmc.fr
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| Phone |
33 1 57274518
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| Organization name |
INSERM U1127-CNRS UMR7225-UPMC
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| Department |
ICM
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| Lab |
Alzheimer and Prions Disease team
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| Street address |
47 boulevard de l'hôpital
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| City |
Paris |
| ZIP/Postal code |
75013 |
| Country |
France |
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| Platforms (1) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA103749 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE9805_RAW.tar |
24.4 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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