Title |
Cure of ADPKD by Selection for Spontaneous Genetic Repair Events in Pkd1-Mutated iPS Cells
|
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Published in |
PLOS ONE, February 2012
|
DOI | 10.1371/journal.pone.0032018 |
Pubmed ID | |
Authors |
Li-Tao Cheng, Shogo Nagata, Kunio Hirano, Shinpei Yamaguchi, Shigeo Horie, Justin Ainscough, Takashi Tada |
Abstract |
Induced pluripotent stem cells (iPSCs) generated by epigenetic reprogramming of personal somatic cells have limited therapeutic capacity for patients suffering from genetic disorders. Here we demonstrate restoration of a genomic mutation heterozygous for Pkd1 (polycystic kidney disease 1) deletion (Pkd1(+/-) to Pkd1(+/R+)) by spontaneous mitotic recombination. Notably, recombination between homologous chromosomes occurred at a frequency of 1~2 per 10,000 iPSCs. Southern blot hybridization and genomic PCR analyses demonstrated that the genotype of the mutation-restored iPSCs was indistinguishable from that of the wild-type cells. Importantly, the frequency of cyst generation in kidneys of adult chimeric mice containing Pkd1(+/R+) iPSCs was significantly lower than that of adult chimeric mice with parental Pkd1(+/-) iPSCs, and indistinguishable from that of wild-type mice. This repair step could be directly incorporated into iPSC development programmes prior to cell transplantation, offering an invaluable step forward for patients carrying a wide range of genetic disorders. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Japan | 1 | 33% |
Unknown | 2 | 67% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 3 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Iran, Islamic Republic of | 1 | 2% |
United States | 1 | 2% |
Saudi Arabia | 1 | 2% |
Unknown | 41 | 93% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 14 | 32% |
Student > Ph. D. Student | 7 | 16% |
Student > Bachelor | 5 | 11% |
Student > Master | 4 | 9% |
Student > Doctoral Student | 2 | 5% |
Other | 8 | 18% |
Unknown | 4 | 9% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 14 | 32% |
Agricultural and Biological Sciences | 11 | 25% |
Biochemistry, Genetics and Molecular Biology | 5 | 11% |
Neuroscience | 4 | 9% |
Psychology | 2 | 5% |
Other | 5 | 11% |
Unknown | 3 | 7% |