Generation of Isogenic Pluripotent Stem Cells Differing Exclusively at Two Early Onset Parkinson Point Mutations

被引：569

作者：

Soldner, Frank ^{[1
]}

Laganiere, Josee ^{[4
]}

Cheng, Albert W. ^{[1
,3
]}

Hockemeyer, Dirk ^{[1
]}

Gao, Qing ^{[1
]}

Alagappan, Raaji ^{[1
]}

Khurana, Vikram ^{[1
,5
,6
]}

Golbe, Lawrence I. ^{[8
]}

Myers, Richard H. ^{[7
]}

Lindquist, Susan ^{[1
,2
]}

Zhang, Lei ^{[4
]}

Guschin, Dmitry ^{[4
]}

Fong, Lauren K. ^{[4
]}

Vu, B. Joseph ^{[4
]}

Meng, Xiangdong ^{[4
]}

Urnov, Fyodor D. ^{[4
]}

Rebar, Edward J. ^{[4
]}

Gregory, Philip D. ^{[4
]}

Zhang, H. Steve ^{[4
]}

Jaenisch, Rudolf ^{[1
,2
]}

机构：

[1] Whitehead Inst, Cambridge, MA 02142 USA

[2] MIT, Dept Biol, Cambridge, MA 02139 USA

[3] MIT, Computat & Syst Biol Program, Cambridge, MA 02139 USA

[4] Sangamo BioSci Inc, Pt Richmond Tech Ctr, Richmond, CA 94804 USA

[5] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA

[6] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA

[7] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA

[8] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurol, New Brunswick, NJ 08903 USA

来源：

CELL | 2011年 / 146卷 / 02期

关键词：

COPY NUMBER; HUMAN ESCS; GENOME; DISEASE; REPAIR; MODEL; OLIGODEOXYNUCLEOTIDES; PATHOGENESIS; GENES; IPSCS;

D O I：

10.1016/j.cell.2011.06.019

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Patient-specific induced pluripotent stem cells (iPSCs) derived from somatic cells provide a unique tool for the study of human disease, as well as a promising source for cell replacement therapies. One crucial limitation has been the inability to perform experiments under genetically defined conditions. This is particularly relevant for late age onset disorders in which in vitro phenotypes are predicted to be subtle and susceptible to significant effects of genetic background variations. By combining zinc finger nuclease (ZFN)-mediated genome editing and iPSC technology, we provide a generally applicable solution to this problem, generating sets of isogenic disease and control human pluripotent stem cells that differ exclusively at either of two susceptibility variants for Parkinson's disease by modifying the underlying point mutations in the a-synuclein gene. The robust capability to genetically correct disease-causing point mutations in patient-derived hiPSCs represents significant progress for basic biomedical research and an advance toward hiPSC-based cell replacement therapies.

引用

页码：318 / 331

页数：14

共 48 条

[1] Reference Maps of Human ES and iPS Cell Variation Enable High-Throughput Characterization of Pluripotent Cell Lines [J].

Bock, Christoph ;

Kiskinis, Evangelos ;

Verstappen, Griet ;

Gu, Hongcang ;

Boulting, Gabriella ;

Smith, Zachary D. ;

Ziller, Michael ;

Croft, Gist F. ;

Amoroso, Mackenzie W. ;

Oakley, Derek H. ;

Gnirke, Andreas ;

Eggan, Kevin ;

Meissner, Alexander .

CELL, 2011, 144 (03) :439-452

[2] A functionally characterized test set of human induced pluripotent stem cells [J].

Boulting, Gabriella L. ;

Kiskinis, Evangelos ;

Croft, Gist F. ;

Amoroso, Mackenzie W. ;

Oakley, Derek H. ;

Wainger, Brian J. ;

Williams, Damian J. ;

Kahler, David J. ;

Yamaki, Mariko ;

Davidow, Lance ;

Rodolfa, Christopher T. ;

Dimos, John T. ;

Mikkilineni, Shravani ;

MacDermott, Amy B. ;

Woolf, Clifford J. ;

Henderson, Christopher E. ;

Wichterle, Hynek ;

Eggan, Kevin .

NATURE BIOTECHNOLOGY, 2011, 29 (03) :279-U147

[3] Modelling schizophrenia using human induced pluripotent stem cells [J].

Brennand, Kristen J. ;

Simone, Anthony ;

Jou, Jessica ;

Gelboin-Burkhart, Chelsea ;

Tran, Ngoc ;

Sangar, Sarah ;

Li, Yan ;

Mu, Yangling ;

Chen, Gong ;

Yu, Diana ;

McCarthy, Shane ;

Sebat, Jonathan ;

Gage, Fred H. .

NATURE, 2011, 473 (7346) :221-+

[4] ALTERING THE GENOME BY HOMOLOGOUS RECOMBINATION [J].

CAPECCHI, MR .

SCIENCE, 1989, 244 (4910) :1288-1292

[5] High-frequency genome editing using ssDNA oligonucleotides with zinc-finger nucleases [J].

Chen, Fuqiang ;

Pruett-Miller, Shondra M. ;

Huang, Yuping ;

Gjoka, Monika ;

Duda, Katarzyna ;

Taunton, Jack ;

Collingwood, Trevor N. ;

Frodin, Morten ;

Davis, Gregory D. .

NATURE METHODS, 2011, 8 (09) :753-U96

[6] Prospects for stem cell-based therapy [J].

Daley, George Q. ;

Scadden, David T. .

CELL, 2008, 132 (04) :544-548

[7] Genetic Animal Models of Parkinson's Disease [J].

Dawson, Ted M. ;

Ko, Han Seok ;

Dawson, Valina L. .

NEURON, 2010, 66 (05) :646-661

[8] Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons [J].

Dimos, John T. ;

Rodolfa, Kit T. ;

Niakan, Kathy K. ;

Weisenthal, Laurin M. ;

Mitsumoto, Hiroshi ;

Chung, Wendy ;

Croft, Gist F. ;

Saphier, Genevieve ;

Leibel, Rudy ;

Goland, Robin ;

Wichterle, Hynek ;

Henderson, Christopher E. ;

Eggan, Kevin .

SCIENCE, 2008, 321 (5893) :1218-1221

[9] Heritable targeted gene disruption in zebrafish using designed zinc-finger nucleases [J].

Doyon, Yannick ;

McCammon, Jasmine M. ;

Miller, Jeffrey C. ;

Faraji, Farhoud ;

Ngo, Catherine ;

Katibah, George E. ;

Amora, Rainier ;

Hocking, Toby D. ;

Zhang, Lei ;

Rebar, Edward J. ;

Gregory, Philip D. ;

Urnov, Fyodor D. ;

Amacher, Sharon L. .

NATURE BIOTECHNOLOGY, 2008, 26 (06) :702-708

[10] Enhancing zinc-finger-nuclease activity with improved obligate heterodimeric architectures [J].

Doyon, Yannick ;

Vo, Thuy D. ;

Mendel, Matthew C. ;

Greenberg, Shon G. ;

Wang, Jianbin ;

Xia, Danny F. ;

Miller, Jeffrey C. ;

Urnov, Fyodor D. ;

Gregory, Philip D. ;

Holmes, Michael C. .

NATURE METHODS, 2011, 8 (01) :74-U108

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