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 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.
Wang
Chi Chiu
CC
Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Shatin, Hong Kong.
Kadota
Mitsutaka
M
Nishigaki
Ryuichi
R
Kazuki
Yasuhiro
Y
Shirayoshi
Yasuaki
Y
Rogers
Michael Scott
MS
Gojobori
Takashi
T
Ikeo
Kazuho
K
Oshimura
Mitsuo
M
D000544:Alzheimer Disease; D000818:Animals; D017209:Apoptosis; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation; D002465:Cell Movement; D002891:Chromosomes, Human, Pair 21; D003599:Cytoskeleton / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology*; D004628:Embryonic Structures; D018628:Gene Dosage; D006801:Humans; D051379:Mice; D005810:Multigene Family; D009474:Neurons / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D014176:Protein Biosynthesis; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism*; D014158:Transcription, Genetic
D018076:DNA, Complementary