Induced pluripotent stem cells with a mitochondrial DNA deletion.
Induced pluripotent stem cells with a mitochondrial DNA deletion.
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DOI：
10.1002/stem.1354
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发表时间：
2013-07
期刊：
影响因子：
5.2
通讯作者：
Agarwal, Suneet
中科院分区：
文献类型：
--
作者：
Cherry, Anne B. C.;Gagne, Katelyn E.;Mcloughlin, Erin M.;Baccei, Anna;Gorman, Bryan;Hartung, Odelya;Miller, Justine D.;Zhang, Jin;Zon, Rebecca L.;Ince, Tan A.;Neufeld, Ellis J.;Lerou, Paul H.;Fleming, Mark D.;Daley, George Q.;Agarwal, Suneet
关键词：
In congenital mitochondrial DNA (mtDNA) disorders, a mixture of normal and mutated mtDNA (termed heteroplasmy) exists at varying levels in different tissues, which determines the severity and phenotypic expression of disease. Pearson marrow pancreas syndrome (PS) is a congenital bone marrow failure disorder caused by heteroplasmic deletions in mtDNA. The cause of the hematopoietic failure in PS is unknown, and adequate cellular and animal models are lacking. Induced pluripotent stem (iPS) cells are particularly amenable for studying mtDNA disorders, as cytoplasmic genetic material is retained during direct reprogramming. Here we derive and characterize iPS cells from a patient with PS. Taking advantage of the tendency for heteroplasmy to change with cell passage, we isolated isogenic PS-iPS cells without detectable levels of deleted mtDNA. We found that PS-iPS cells carrying a high burden of deleted mtDNA displayed differences in growth, mitochondrial function, and hematopoietic phenotype when differentiated in vitro, compared to isogenic iPS cells without deleted mtDNA. Our results demonstrate that reprogramming somatic cells from patients with mtDNA disorders can yield pluripotent stem cells with varying burdens of heteroplasmy that might be useful in the study and treatment of mitochondrial diseases.
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影响因子：
4
作者：
DiMauro, Salvatore
通讯作者：
DiMauro, Salvatore
影响因子：
64.8
作者：
Park, In-Hyun;Zhao, Rui;Daley, George Q.
通讯作者：
Daley, George Q.
影响因子：
3.7
作者：
Varum S;Rodrigues AS;Moura MB;Momcilovic O;Easley CA 4th;Ramalho-Santos J;Van Houten B;Schatten G
通讯作者：
Schatten G
影响因子：
5.2
作者：
van den Ouweland, JMW;de Klerk, JBC;Maassen, JA
通讯作者：
Maassen, JA
DOI：
10.1073/pnas.92.14.6562
发表时间：
1995-07-03
影响因子：
11.1
作者：
DUNBAR, DR;MOONIE, PA;HOLT, IJ
通讯作者：
HOLT, IJ