{
  "abstract": "Mitochondrial DNA (mtDNA) heteroplasmy is a significant source of cellular genetic diversity and can cause disease yet its distribution and functional importance across different human cell types are poorly understood. Here we present scMOCHA (Single-Cell Mitochondrial Omics for Cellular Heteroplasmy Analysis), a scalable computational framework that resolves highconfidence, single-cell resolution mtDNA heteroplasmy directly from standard single-cell RNA sequencing (scRNA-seq) data. Using this tool to interrogate publicly available scRNA-seq datasets from human peripheral blood mononuclear cells (PBMC) and bone marrow (BM) uncovered the single-cell landscape of mtDNA single-nucleotide variants (SNVs) and heteroplasmy across ages in human hematopoietic cell types. PBMCs and BM share many inherited homoplasmic and highly heteroplasmic SNVs, whereas somatic SNVs are tissue- and cell type-specific and distributed across the mtDNA genome, suggesting that they arise largely stochastically. mtDNA replication error is a dominant force shaping homoplasmic variants, while oxidative stress potentially drives a significant portion of heteroplasmic and somatic mutations. Importantly, we discover previously unknown cell type-specific and human disease-associated mtDNA SNVs. By coupling mtDNA genotypes with matched single-cell nuclear transcriptomes and structural modeling, we uncover potential molecular mechanisms by which disease-associated mtDNA SNVs impact cellular processes such as inflammation and contribute to disease. Together, these findings define the single-cell variant landscape of the human mitochondrial genome and reveal previously unrecognized lineage- and disease-associated patterns of mtDNA variation in the human hematopoietic system.",
  "abstract_shown": true,
  "affiliations": [
    "Children's Hospital of Philadelphia and University of Pennsylvania"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "name": "C. Liu"
    },
    {
      "name": "T. Peng"
    },
    {
      "name": "Z. Cen"
    },
    {
      "name": "P. Lu"
    },
    {
      "name": "P. Potluri"
    },
    {
      "name": "P. Hu"
    },
    {
      "name": "S. Zhang"
    },
    {
      "name": "M. T. Lott"
    },
    {
      "name": "G. Widjaja"
    },
    {
      "name": "D. C. Wallace"
    },
    {
      "name": "Y. Xing"
    },
    {
      "affs": [
        0
      ],
      "name": "L. Pei"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bv1z15tjtkfj7.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.11.758340",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.11.758340v1.full",
  "id": "bv1z15tjtkfj7",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.11.758340v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "genetics"
    ],
    [
      "openalex",
      "1312|Mitochondrial Function and Pathology"
    ]
  ],
  "openalex": "W7221680716",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.11.758340v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-11",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/bv1z15tjtkfj7.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:27:28Z",
      "native_id": "10.64898/2026.10.11.758340",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.11.758340v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:genetics",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "Single-cell variant landscape of the human mitochondrial genome reveals cell type-specific functions and disease mechanisms",
  "title_text": "Single-cell variant landscape of the human mitochondrial genome reveals cell type-specific functions and disease mechanisms",
  "type": "preprint",
  "updated_at": "2026-10-30T12:27:28Z",
  "url": "https://research.draconitic.com/paper/bv1z15tjtkfj7",
  "venue": "bioRxiv",
  "versions": []
}