Derivation of Huntington's Disease-Affected Human Embryonic Stem Cell Lines

被引：47

作者：

Bradley, Cara K. ^{[1
]}

Scott, Heather A. ^{[1
]}

Chami, Omar ^{[1
]}

Peura, Teija T. ^{[1
]}

Dumevska, Biljana ^{[1
]}

Schmidt, Uli ^{[1
]}

Stojanov, Tomas ^{[1
]}

机构：

[1] Sydney IVF Stem Cells, Sydney, NSW 2000, Australia

来源：

STEM CELLS AND DEVELOPMENT | 2011年 / 20卷 / 03期

关键词：

CAG REPEAT; DRUG DISCOVERY; IN-VITRO; LENGTH; GENE; MODELS; NEURODEGENERATION; DIFFERENTIATION; INACTIVATION; POLYMORPHISM;

D O I：

10.1089/scd.2010.0120

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by an expansion of cytosine-adenine-guanine (CAG) repeats in the Huntingtin gene Htt. To facilitate research into HD, we have derived 4 human embryonic stem cell (hESC) lines containing >= 40CAG repeats in exon 1 of Htt: SIVF017-HD (CAG(40)), SIVF018-HD (CAG(46)), SIVF020-HD (CAG(48)), and SIVF046-HD (CAG(45)). Additionally, we have derived a normal sibling-matched control for SIVF020-HD, cell line SIVF019. All 5 hESC lines had a normal karyotype, expressed pluripotency markers including Oct4, SSEA3, and Tra-1-81, and could be maintained in culture for multiple (>40) passages. Teratoma studies revealed that the hESC lines were capable of differentiating into cells representative of the 3 germ layers. Furthermore, in vitro neuronal differentiation experiments have confirmed that the hESC lines were able to generate MAP2-positive neuronal cells that express the Htt protein. Combined, these experiments confirm that the cell lines represent pluripotent stem cell lines. These HD-affected hESC lines will be made available to biomedical research laboratories and will provide a valuable tool to investigate the mechanisms and potential treatments for HD.

引用

页码：495 / 502

页数：8

共 46 条

[31] Mutation analysis and association studies of the ubiquitin carboxyterminal hydrolase L1 gene in Huntington's disease [J].