Proteomic signatures and aberrations of mouse embryonic stem cells containing a single human chromosome 21 in neuronal differentiation: an in vitro model of Down syndrome.
Neurodegeneration in fetal development of Down syndrome (DS) patients is proposed to result in apparent neuropathological abnormalities and to contribute to the phenotypic characteristics of mental retardation and premature development of Alzheimer disease. In order to identify the aberrant and specific genes involved in the early differentiation of DS neurons, we have utilized an in vitro neuronal differentiation system of mouse ES cells containing a single human chromosome 21 (TT2F/hChr21) with TT2F parental ES cells as a control. The paired protein extracts from TT2F and TT2F/hChr21 cells at several stages of neuronal differentiation were subjected to two-dimensional polyacrylamide gel electrophoresis protein separation followed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry to identify the proteins differentially expressed between TT2F and TT2F/hChr21 cells. We provide here a novel set of specific gene products altered in early differentiating DS neuronal cells, which differs from that identified in adult or fetal brain with DS. The aberrant protein expression in early differentiating neurons, due to the hChr21 gene dosage effects or chromosomal imbalance, may affect neuronal outgrowth, proliferation and differentiation, producing developmental abnormalities in neural patterning, which eventually leads to formation of a suboptimal functioning neuronal network in DS.
Kadota
M
M
Department of Human Genome Science (Kirin Brewery), Graduate School of Medical Science, Tottori University, 86 Nishimachi, Yonago, Tottori 683-8503, Japan.
Nishigaki
R
R
Wang
C C
CC
Toda
T
T
Shirayoshi
Y
Y
Inoue
T
T
Gojobori
T
T
Ikeo
K
K
Rogers
M S
MS
Oshimura
M
M
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D002869:Chromosome Aberrations; D002891:Chromosomes, Human, Pair 21 / Q000648:ultrastructure*; D004314:Down Syndrome / Q000235:genetics* / Q000648:ultrastructure*; D015536:Down-Regulation; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D051379:Mice; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure*; D040901:Proteomics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013234:Stem Cells / Q000378:metabolism*; D015854:Up-Regulation
D009419:Nerve Tissue Proteins; D012333:RNA, Messenger