ArticleThe New England journal of medicine2020
Purifying Selection against Pathogenic Mitochondrial DNA in Human T Cells.
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Article in The New England journal of medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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69citing papers in PubMed
4.8field-weighted citation impact, top 4% of its field
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Who cites it
69 citing papers in PubMed, 94 citations in OpenAlex.
- Understanding the somatic evolution of metabolic traits.Nature metabolism · 2026Article
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- Single-cell Omics Assessment of Mitochondrial Function: Current Status and Future Perspectives.Genomics, proteomics & bioinformatics · 2026Review
- Mitochondrial cardiomyopathy: bridging molecular mechanisms and clinical frontiers.Nature reviews. Cardiology · 2026Review
- Mechanisms and disease relevance of mitochondrial translation in humans.Nature reviews. Molecular cell biology · 2026Review
- MitoPerturb-Seq identifies gene-specific single-cell responses to mitochondrial DNA depletion and heteroplasmy.Nature structural & molecular biology · 2026Article
- Detection of mitochondrial DNA mutations in T cells following 5-FU or cisplatin exposure.Cell reports. Medicine · 2026Article
- Single-cell multi-omic analysis of mitochondrial mutational mosaicism and dynamics.Nature communications · 2026Article
- Immune Cell Mitochondrial Phenotypes Are Largely Preserved in Mitochondrial Diseases and Do Not Reflect Disease Severity.Neurology. Genetics · 2026Article
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- Functionally dominant hotspot mutations of mitochondrial ribosomal RNA genes in cancer.Nature genetics · 2025Article
- Biological and translational attributes of mitochondrial DNA copy number: Laboratory perspective to clinical relevance.World journal of methodology · 2025Review
- Pervasive non-random mitochondrial DNA heteroplasmy in the hybrid water frog Pelophylax esculentus.BMC ecology and evolution · 2025Article
- Intergenerational Enlargement of Human Organs as a Driver of Increased Cancer Risk?BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Tipping the balance: innate and adaptive immunity in mitochondrial disease.Current opinion in immunology · 2025Review
- Understanding the impact of mitochondrial DNA mutations on aging and carcinogenesis (Review).International journal of molecular medicine · 2025Review
- Cell type-specific purifying selection of synonymous mitochondrial DNA variation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Age-dependent accumulation of mitochondrial tRNA mutations in mouse kidneys linked to mitochondrial kidney diseases.Nature aging · 2025Article
- Selfish mutations promote age-associated erosion of mtDNA integrity in mammals.Nature communications · 2025Article
- Article
9 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Melissa A WalkerFrom 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.
Caleb A LareauFrom 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.
Leif S LudwigFrom 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.
Amel KaraaFrom 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.
Vijay G SankaranFrom 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.
Aviv RegevFrom 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.
Vamsi K MoothaFrom 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.ORCID 0000-0001-9924-642X
Howard Hughes Medical Institute · USBoston Children's Hospital · US
Funding
The Harvard Clinical and Translational Science CenterUL1TR002541 · NCATS · HARVARD MEDICAL SCHOOL · PI NADLER, LEE MARSHALL · 2018 to 2022
$93.0MCenter for Cell CircuitsRM1HG006193 · NHGRI · BROAD INSTITUTE, INC. · PI BLAINEY, PAUL CLARK, HACOHEN, NIR · 2016 to 2020
$14.9MSystematic Genetic Dissection of Human ErythropoiesisR01DK103794 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI Vijay Ganesh Sankaran · 2014 to 2026
$5.9MHoward Hughes Medical InstituteNHGRI NIH HHS RM1 HG006193NIDDK NIH HHS R01 DK103794
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.).
Indexed as
MutationPolymorphism, GeneticT-LymphocytesAdultDNA, MitochondrialGenome, MitochondrialHumansLeukocytes, MononuclearMaleMELAS SyndromeMiddle AgedDNA, Mitochondrial
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