Molecular hierarchy in neurons differentiated from mouse ES cells containing a single human chromosome 21

Defects in neurogenesis and neuronal differentiation in the fetal brain of Down syndrome (DS) patients lead to the apparent neuropathological abnormalities and contribute to the phenotypic characters of mental retardation, and premature development of Alzheimer’s disease, those being the most common...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2004-02, Vol.314 (2), p.335-350
Main Authors: Wang, Chi Chiu, Kadota, Mitsutaka, Nishigaki, Ryuichi, Kazuki, Yasuhiro, Shirayoshi, Yasuaki, Rogers, Michael Scott, Gojobori, Takashi, Ikeo, Kazuho, Oshimura, Mitsuo
Format: Article
Language:English
Subjects:
Alzheimer Disease
Animals
Apoptosis
cDNA microarray
Cell Culture Techniques - methods
Cell Differentiation
Cell Movement
Chromosomes, Human, Pair 21
Cytoskeleton - metabolism
DNA, Complementary - metabolism
Down syndrome
Embryo, Mammalian - cytology
Embryonic Structures
ES cells
Gene Dosage
Humans
Mice
Multigene Family
Neurons - metabolism
Oligonucleotide Array Sequence Analysis
Phenotype
Protein Biosynthesis
SDIA
Signal Transduction
Stem Cells - metabolism
Transcription, Genetic
TT2F/hChr21 clones
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Summary:Defects in neurogenesis and neuronal differentiation in the fetal brain of Down syndrome (DS) patients lead to the apparent neuropathological abnormalities and contribute to the phenotypic characters of mental retardation, and premature development of Alzheimer’s disease, those being the most common phenotype in DS. In order to understand the molecular mechanism underlying the cause of phenotypic abnormalities in the DS brain, we have utilized an in vitro model of TT2F mouse embryonic stem cells containing a single human chromosome 21 (hChr21) to study neuron development and neuronal differentiation by microarray containing 15K developmentally expressed cDNAs. Defective neuronal differentiation in the presence of extra hChr21 manifested primarily the post-transcriptional and translational modification, such as Mrpl10, SNAPC3, Srprb, SF3a60 in the early neuronal stem cell stage, and Mrps18a, Eef1g, and Ubce8 in the late differentiated stage. Hierarchical clustering patterned specific expression of hChr21 gene dosage effects on neuron outgrowth, migration, and differentiation, such as Syngr2, Dncic2, Eif3sf, and Peg3.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2003.12.091