標題: Modeling neurogenesis impairment in down syndrome with induced pluripotent stem cells from Trisomy 21 amniotic fluid cells
作者: Lu, Huai-En
Yang, Yao-Chen
Chen, Sheng-Mei
Su, Hong-Lin
Huang, Pai-Cheng
Tsai, Ming-Song
Wang, Tzu-Hao
Tseng, Ching-Ping
Hwang, Shiaw-Min
生物科技學系
Department of Biological Science and Technology
關鍵字: Down syndrome;Trisomy 21;Neurogenesis impairment;Induced pluripotent stem cells;miRNA
公開日期: 15-二月-2013
摘要: Down syndrome (DS), or Trisomy 21 (121) syndrome, one of the most common chromosomal abnormalities, is caused by an extra duplication of chromosome 21. In studies of neuron development, experimental models based on human cells are considered to be the most desired and accurate for basic research. The generation of diseased induced pluripotetn stem (iPS) cell is a critical step in understanding the developmental stages of complex neuronal diseases. Here, we generated human DS iPS cell lines from second trimester amniotic fluid (AF) cells with 121 by co-expressing Yamanaka factors through lentiviral delivery and subsequently differentiated them into neuronal progenitor cells (NPCs) for further analyses. 121 AF-iPS cells were characterized for the expression of pluripotent markers and for their ability to differentiate into all three germ layers by forming embryoid bodies in vitro and teratomas in vivo. The 121 AF-iPS cells maintained their unique pattern of chromosomal karyotypes: three pairs of chromosome 21. The level of amyloid precursor protein was significantly increased in NPCs derived from 121 AF-iPS cells compared with NPCs from normal AF-iPS cells. The expression levels of miR-155 and miR-802 in 121 AF-iPS-NPCs were highly elevated in the presence of low expression of MeCP2. We observed that 121 iPS-NPCs generated fewer neurons compared with controls. 121 iPS-NPCs exhibit developmental defects during neurogenesis. Our findings suggest that 121 AF-iPS cells serve as a good source to further elucidate the impairment neurogenesis of DS and the onset of Alzheimer's disease. (C) 2012 Elsevier Inc. All rights reserved.
URI: http://dx.doi.org/10.1016/j.yexcr.2012.09.017
http://hdl.handle.net/11536/21212
ISSN: 0014-4827
DOI: 10.1016/j.yexcr.2012.09.017
期刊: EXPERIMENTAL CELL RESEARCH
Volume: 319
Issue: 4
起始頁: 498
結束頁: 505
顯示於類別:期刊論文


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  1. 000315067800013.pdf