Open AccessInduced Pluripotent Stem Cells with a Mitochondrial DNA Deletion
Author(s) -
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
Publication year - 2013
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.1354
Subject(s) - heteroplasmy , biology , induced pluripotent stem cell , reprogramming , mitochondrial dna , somatic cell , stem cell , genetics , phenotype , microbiology and biotechnology , haematopoiesis , mitochondrial disease , cell , embryonic stem cell , gene
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. S TEM C ELLS 2013;31:1287–1297