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

Chi Chiu Wang, Mitsutaka Kadota, Ryuichi Nishigaki, Yasuhiro Kazuki, Yasuaki Shirayoshi, Michael Scott Rogers, Takashi Gojobori, Kazuho Ikeo, Mitsuo Oshimura

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)335-350
Number of pages16
JournalBiochemical and Biophysical Research Communications
Issue number2
Publication statusPublished - 2004 Feb 6

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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