From the Departments of Molecular Biology (M.A.W., V.K.M.), Neurology (M.A.W.), and Medicine (V.K.M) and the Genetics Unit, Department of Pediatrics (A.K.), Massachusetts General Hospital, Howard Hughes Medical Institute (M.A.W., A.R., V.K.M.), the Division of Hematology-Oncology, Boston Children's Hospital (C.A.L., L.S.L., V.G.S.), the Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School (C.A.L., L.S.L., V.G.S.), the Department of Systems Biology, Harvard Medical School (V.K.M.), and Harvard Medical School (M.A.W., A.K.), Boston, and the Klarman Cell Observatory (L.S.L., A.R.), Broad Institute of MIT (Massachusetts Institute of Technology) and Harvard (M.A.W., C.A.L., V.G.S., V.K.M.), the Harvard Stem Cell Institute (V.G.S.), and the Department of Biology and Koch Institute of Integrative Cancer Research, Massachusetts Institute of Technology (A.R.), Cambridge - both in Massachusetts.
N Engl J Med. 2020 Oct 15;383(16):1556-1563. doi: 10.1056/NEJMoa2001265. Epub 2020 Aug 12.
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.).
许多线粒体疾病是由线粒体 DNA（mtDNA）突变引起的。患者的细胞中含有突变型和非突变型 mtDNA 的混合物（称为异质性）。突变型 mtDNA 的比例在不同患者和同一患者的不同组织之间有所不同。我们同时检测了来自三位无关联的线粒体脑肌病伴乳酸酸中毒和卒中样发作患者的数千个血细胞中的单细胞异质性和细胞状态，这些患者都携带 A3243G 相关的突变。我们观察到所有细胞类型中存在广泛的异质性，但也发现 T 细胞中的异质性明显降低，这一发现与该谱系内的纯化选择一致。我们在另外六位没有卒中样发作的携带 A3243G 异质性的患者中观察到了这种模式。（由万豪基金会等资助）。
