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

[1] A CCG REPEAT POLYMORPHISM ADJACENT TO THE CAG REPEAT IN THE HUNTINGTON DISEASE GENE - IMPLICATIONS FOR DIAGNOSTIC-ACCURACY AND PREDICTIVE TESTING [J].

ANDREW, SE ;

GOLDBERG, YP ;

THEILMANN, J ;

ZEISLER, J ;

HAYDEN, MR .

HUMAN MOLECULAR GENETICS, 1994, 3 (01) :65-67

[2] THE RELATIONSHIP BETWEEN TRINUCLEOTIDE (CAG) REPEAT LENGTH AND CLINICAL-FEATURES OF HUNTINGTONS-DISEASE [J].

ANDREW, SE ;

GOLDBERG, YP ;

KREMER, B ;

TELENIUS, H ;

THEILMANN, J ;

ADAM, S ;

STARR, E ;

SQUITIERI, F ;

LIN, BY ;

KALCHMAN, MA ;

GRAHAM, RK ;

HAYDEN, MR .

NATURE GENETICS, 1993, 4 (04) :398-403

[3] Striatal progenitors derived from human ES cells mature into DARPP32 neurons in vitro and in quinolinic acid-lesioned rats [J].

Aubry, Laetitia ;

Bugi, Aurore ;

Lefort, Nathalie ;

Rousseau, France ;

Peschanski, Marc ;

Perrier, Anselme L. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (43) :16707-16712

[4] Normal and mutant HTT interact to affect clinical severity and progression in Huntington disease [J].

Aziz, N. A. ;

Jurgens, C. K. ;

Landwehrmeyer, G. B. ;

van Roon-Mom, W. M. C. ;

van Ommen, G. J. B. ;

Stijnen, T. ;

Roos, R. A. C. ;

Orth, M. ;

Handley, O. J. ;

Schwenke, C. ;

Ho, A. ;

Wild, E. J. ;

Tabrizi, S. J. ;

Landwehrmeyer, G. B. ;

Bachoud-Levi, A-C ;

Bentivoglio, A. R. ;

Biunno, I. ;

Bonelli, R. ;

Burgunder, J-M ;

Dunnett, S. B. ;

Ferreira, J. J. ;

Handley, O. J. ;

Heiberg, A. ;

Illman, T. ;

Levey, J. ;

Nielsen, J. E. ;

Paivarinta, M. ;

Roos, R. A. C. ;

Sebastian, A. Rojo ;

Tabrizi, S. J. ;

Vandenberghe, W. ;

Verellen-Dumoulin, C. ;

Zaremba, J. ;

Uhrova, T. ;

Wahlstrom, J. ;

Wallner, M. ;

Barth, K. ;

Garde, M. Bascunana ;

Bos, R. ;

Ecker, D. ;

Handley, O. J. ;

Heinonen, N. ;

Held, C. ;

Laura, M. ;

Descals, A. Martinez ;

Mestre, T. ;

Monza, D. ;

Naji, J. ;

Padieu, H. ;

Koivisto, S. Pro .

NEUROLOGY, 2009, 73 (16) :1280-1285

[5]

Brinkman RR, 1997, AM J HUM GENET, V60, P1202

[6] Endless Possibilities: Stem Cells and the Vision for Toxicology Testing in the 21st Century [J].

Chapin, Robert E. ;

Stedman, Donald B. .

TOXICOLOGICAL SCIENCES, 2009, 112 (01) :17-22

[7] Human Stem Cells for Modeling Neurological Disorders: Accelerating the Drug Discovery Pipeline [J].

Crook, Jeremy Micah ;

Kobayashi, Nao Rei .

JOURNAL OF CELLULAR BIOCHEMISTRY, 2008, 105 (06) :1361-1366

[8] Increased cell proliferation and neurogenesis in the adult human Huntington's disease brain [J].

Curtis, MA ;

Penney, EB ;

Pearson, AG ;

van Roon-Mom, WMC ;

Butterworth, NJ ;

Dragunow, M ;

Connor, B ;

Faull, RLM .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (15) :9023-9027

[9] Embryonic stem cells: a promising tool for cell replacement therapy [J].

Doss, MX ;

Koehler, CI ;

Gissel, C ;

Hescheler, J ;

Sachinidis, A .

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2004, 8 (04) :465-473

[10] Inactivation of Hdh in the brain and testis results in progressive neurodegeneration and sterility in mice [J].

Dragatsis, I ;

Levine, MS ;

Zeitlin, S .

NATURE GENETICS, 2000, 26 (03) :300-306

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