许多线粒体疾病是由线粒体DNA（mtDNA）突变引起的。患者的细胞包含突变和非突变mtDNA的混合物（一种称为异质性的现象）。突变mtDNA的比例在患者之间以及患者体内的组织之间有较大差异。研究组同时检测了来自三个无关患者的数千个血细胞的单细胞异质性和细胞状态，这些患者有A3243G相关的线粒体脑肌病、乳酸性酸中毒和中风样发作。

研究组观察到所有细胞类型均有广泛异质性，但也发现T细胞的异质性显著降低，这与该谱系中的纯化选择一致。研究组在另外6例异质性A3243G无卒中样发作的患者中也观察到了这种模式。

附：英文原文

Title: Purifying Selection against Pathogenic Mitochondrial DNA in Human T Cells

Author: Melissa A. Walker, M.D., Ph.D.,, Caleb A. Lareau, Ph.D.,, Leif S. Ludwig, M.D., Ph.D.,, Amel Karaa, M.D.,, Vijay G. Sankaran, M.D., Ph.D.,, Aviv Regev, Ph.D.,, and Vamsi K. Mootha, M.D.

Issue&Volume: 2020-08-12

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.

DOI: 10.1056/NEJMoa2001265

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2001265