Volume 19, No 2, Feb 2009
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 19 Issue 2, February 2009: 247-258
ORIGINAL ARTICLES
Enhanced apoptosis during early neuronal differentiation in mouse ES cells with autosomal imbalance
Yoshiteru Kai2, Chi Chiu Wang2, Satoshi Kishigami3, Yasuhiro Kazuki1, Satoshi Abe1, Masato Takiguchi1, Yasuaki Shirayoshi1, Toshiaki Inoue1, Hisao Ito4, Teruhiko Wakayama3 and Mitsuo Oshimura1
1Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan
2Department of Obstetrics and Gynaecology & Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Shatin New Territories, Hong Kong SAR, China
3Laboratory for Genomic Reprogramming Center for Developmental Biology, RIKEN, 2-2-3 Minatojima Minamimachi Chuo-ku, Kobe, Hyogo 650-0047, Japan
4Division of Organ Pathology, Department of Microbiology and Pathology, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan
Correspondence: Mitsuo Oshimura,(oshimura@grape.med.tottori-u.ac.jp)
Although particular chromosomal syndromes are phenotypically and clinically distinct, the majority of individuals with autosomal imbalance, such as aneuploidy, manifest mental retardation. A common abnormal phenotype of Down syndrome (DS), the most prevalent autosomal aneuploidy, shows a reduction in both the number and the density of neurons in the brain. As a DS model, we have recently created chimeric mice from ES cells containing a single human chromosome 21. The mice mimicked the characteristic phenotypic features of DS, and ES cells showed a higher incidence of apoptosis during early neuronal differentiation in vitro. In this study, we examined the induction of anomalous early neural development by aneuploidy in mouse ES cells by transferring various human chromosomes or additional mouse chromosomes. Results showed an elevated incidence of apoptosis in all autosome-aneuploid clones examined during early neuronal differentiation in vitro. Further, cDNA microarray analysis revealed a common cluster of down-regulated genes, of which eight known genes are related to cell proliferation, neurite outgrowth and differentiation. Importantly, targeting of these genes by siRNA knockdown in normal mouse ES cells led to enhanced apoptosis during early neuronal differentiation. These findings strongly suggest that autosomal imbalance is associated with general neuronal loss through a common molecular mechanism for apoptosis.
Cell Research (2009) 19:247-258. doi: 10.1038/cr.2008.305; published online 18 November 2008
FULL TEXT | PDF
Browse 1801
