Year: 2020
Type: article
Abstract: Many mitochondrial diseases are caused by mutations in mitochondrial DNA (mtDNA). Patients' cells contain a mixture of mutant and nonmutant mtDNA (a phenomenon called heteroplasmy). The proportion of mutant mtDNA varies across patients and among tissues within a patient. We simultaneously assayed single-cell heteroplasmy and cell state in thousands of blood cells obtained from three unrelated patients who had A3243G-associated mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes. We observed a broad range of heteroplasmy across all cell types but also found markedly reduced heteroplasmy in T cells, a finding consistent with purifying selection within this lineage. We observed this pattern in six additional patients who had heteroplasmic A3243G without strokelike episodes. (Funded by the Marriott Foundation and others.).
Source: New England Journal of Medicine
Institutions: Boston Children's Hospital, Howard Hughes Medical Institute, Harvard University, Massachusetts General Hospital, Dana-Farber Cancer Institute, Dana-Farber/Harvard Cancer Center, Klarman Cell Observatory, Harvard Stem Cell Institute, Koch Institute for Integrative Cancer Research At MIT, Massachusetts Institute of Technology
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
Funders: Howard Hughes Medical Institute, New York Stem Cell Foundation, Massachusetts General Hospital, J. Willard and Alice S. Marriott Foundation, National Institutes of Health, Klarman Cell Observatory, Broad Institute, National Human Genome Research Institute, National Institute of Diabetes and Digestive and Kidney Diseases
OpenAlex ID: W3048604725