Evidence map›Paper›PMID 30827679›Full record

ArticleCell2019

Lineage Tracing in Humans Enabled by Mitochondrial Mutations and Single-Cell Genomics.

Leif S Ludwig, Caleb A Lareau, Jacob C Ulirsch, Elena Christian, Christoph Muus, Lauren H Li, Karin Pelka, Will Ge, Yaara Oren, Alison Brack and 10 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 325 papers.

0numbers the graph read from it
0cells of the map it votes in
325citing papers in PubMed
28.9field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

325 citing papers in PubMed, 546 citations in OpenAlex.

  1. Review
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  6. Clonal selection of somatic mutations shapes NK cell memory.bioRxiv : the preprint server for biology · 2026
    Article
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265 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 2 institutions in 1 country.

Leif S LudwigBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA. Electronic address: ludwig@broadinstitute.org.
Caleb A LareauBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA 02129, USA; Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115, USA.
Jacob C UlirschBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115, USA.
Elena ChristianBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Christoph MuusBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
Lauren H LiBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Karin PelkaBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Will GeBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Yaara OrenBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Alison BrackBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Travis LawBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Christopher RodmanBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Jonathan H ChenBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA.
Genevieve M BolandCenter for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Nir HacohenBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Orit Rozenblatt-RosenBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Martin J AryeeBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA 02129, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
Jason D BuenrostroBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Society of Fellows, Harvard University, Cambridge, MA 02138, USA.
Aviv RegevBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Department of Biology and Koch Institute of Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: aregev@broadinstitute.org.
Vijay G SankaranBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA. Electronic address: sankaran@broadinstitute.org.
Broad Institute · USHarvard University · US

Funding

Center for Cell CircuitsRM1HG006193 · NHGRI · BROAD INSTITUTE, INC. · PI BLAINEY, PAUL CLARK, HACOHEN, NIR · 2016 to 2020
$14.9M
Molecular, Cellular, & Developmental Dynamics PhD ProgramT32GM007226 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI VAN VACTOR, DAVID L. · 1985 to 2021
$14.4M
Systematic Genetic Dissection of Human ErythropoiesisR01DK103794 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI Vijay Ganesh Sankaran · 2014 to 2026
$5.9M
(PQ3) The role of damaged DNA in inter-individual variation of tumor immunityR01CA208756 · NCI · BROAD INSTITUTE, INC. · PI HACOHEN, NIR · 2016 to 2020
$2.6M
Cancer Immunology Training GrantT32CA207021 · NCI · DANA-FARBER CANCER INST · PI WUCHERPFENNIG, KAI W · 2016 to 2020
$2.4M
An integrated multiplexed genomic assay for low input clinical samples1U24AI118672 · NIAID · BROAD INSTITUTE, INC. · PI SHALEK, ALEX K · 2015 to 2019
$2.0M
Identifying Genome-wide Association Study-Nominated Regulators of ErythropoiesisR33HL120791 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI SANKARAN, VIJAY GANESH · 2016 to 2018
$1.7M
Clinical implementation of single cell tumor transcriptome analysisR33CA202820 · NCI · BROAD INSTITUTE, INC. · PI GOLUB, TODD R., JOHNSON, BRUCE E. · 2016 to 2018
$1.3M
Charting somatic evolution via single-cell multiomicsK99HG012579 · NHGRI · STANFORD UNIVERSITY · PI LAREAU, CALEB ANDREW · 2022 to 2022
$119k
Inference of variable chromatin loops in glioblastoma tumors and single-cellsF31CA232670 · NCI · HARVARD MEDICAL SCHOOL · PI LAREAU, CALEB ANDREW · 2018 to 2019
$63k
Howard Hughes Medical InstituteNCI NIH HHS F31 CA232670NCI NIH HHS R01 CA208756NCI NIH HHS R33 CA202820NCI NIH HHS T32 CA207021NHGRI NIH HHS K99 HG012579NHGRI NIH HHS RM1 HG006193NHLBI NIH HHS R33 HL120791NIAID NIH HHS U24 AI118672NIDDK NIH HHS R01 DK103794NIGMS NIH HHS T32 GM007226
6 · The paper itself

Abstract

Lineage tracing provides key insights into the fate of individual cells in complex organisms. Although effective genetic labeling approaches are available in model systems, in humans, most approaches require detection of nuclear somatic mutations, which have high error rates, limited scale, and do not capture cell state information. Here, we show that somatic mutations in mtDNA can be tracked by single-cell RNA or assay for transposase accessible chromatin (ATAC) sequencing. We leverage somatic mtDNA mutations as natural genetic barcodes and demonstrate their utility as highly accurate clonal markers to infer cellular relationships. We track native human cells both in vitro and in vivo and relate clonal dynamics to gene expression and chromatin accessibility. Our approach should allow clonal tracking at a 1,000-fold greater scale than with nuclear genome sequencing, with simultaneous information on cell state, opening the way to chart cellular dynamics in human health and disease.

Indexed as

Base SequenceCell LineageChromatinColorectal NeoplasmsDNA, MitochondrialGenomicsHEK293 CellsHematopoietic Stem CellsHigh-Throughput Nucleotide SequencingHumansMitochondriaMutationSingle-Cell AnalysisTransposasesChromatinDNA, MitochondrialTransposaseschronic myeloid leukemiacolon cancerhematopoiesislineage tracingmitochondrial DNAmtDNAsequencingsingle cell genomicssomatic mutations

Identifiers

PMID30827679
PMCPMC6408267
OpenAlexW2919632356

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.