Modeling neurogenesis impairment in down syndrome with induced pluripotent stem cells from Trisomy 21 amniotic fluid cells

Huai En Lu, Yao Chen Yang, Sheng Mei Chen, Hong Lin Su, Pai Cheng Huang, Ming Song Tsai, Tzu Hao Wang, Ching-Ping Tseng*, Shiaw Min Hwang

*此作品的通信作者

研究成果: Article同行評審

57 引文 斯高帕斯(Scopus)

摘要

Down syndrome (DS), or Trisomy 21 (T21) 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 T21 by co-expressing Yamanaka factors through lentiviral delivery and subsequently differentiated them into neuronal progenitor cells (NPCs) for further analyses. T21 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 T21 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 T21 AF-iPS cells compared with NPCs from normal AF-iPS cells. The expression levels of miR-155 and miR-802 in T21 AF-iPS-NPCs were highly elevated in the presence of low expression of MeCP2. We observed that T21 iPS-NPCs generated fewer neurons compared with controls. T21 iPS-NPCs exhibit developmental defects during neurogenesis. Our findings suggest that T21 AF-iPS cells serve as a good source to further elucidate the impairment neurogenesis of DS and the onset of Alzheimer's disease.

原文English
頁(從 - 到)498-505
頁數8
期刊Experimental Cell Research
319
發行號4
DOIs
出版狀態Published - 15 2月 2013

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