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Identification of leukemic and pre-leukemic stem cells by clonal tracking from single-cell transcriptomics

Author

Listed:
  • Lars Velten

    (Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology
    Universitat Pompeu Fabra (UPF))

  • Benjamin A. Story

    (European Molecular Biology Laboratory (EMBL), Genome Biology Unit
    Swiss Federal Institute of Technology (ETH) Zurich, Department of Biosystems Science and Engineering)

  • Pablo Hernández-Malmierca

    (Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH)
    Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ) and DKFZ-ZMBH Alliance)

  • Simon Raffel

    (Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH)
    Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ) and DKFZ-ZMBH Alliance
    University of Heidelberg)

  • Daniel R. Leonce

    (European Molecular Biology Laboratory (EMBL), Genome Biology Unit)

  • Jennifer Milbank

    (European Molecular Biology Laboratory (EMBL), Genome Biology Unit)

  • Malte Paulsen

    (European Molecular Biology Laboratory (EMBL), Flow Cytometry Core Facility)

  • Aykut Demir

    (University of Heidelberg)

  • Chelsea Szu-Tu

    (Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology
    Universitat Pompeu Fabra (UPF))

  • Robert Frömel

    (Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology
    Universitat Pompeu Fabra (UPF))

  • Christoph Lutz

    (University of Heidelberg)

  • Daniel Nowak

    (Medical Faculty Mannheim, Heidelberg University)

  • Johann-Christoph Jann

    (Medical Faculty Mannheim, Heidelberg University)

  • Caroline Pabst

    (University of Heidelberg
    University of Heidelberg and European Molecular Biology Laboratory (EMBL))

  • Tobias Boch

    (Swiss Federal Institute of Technology (ETH) Zurich, Department of Biosystems Science and Engineering
    Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ) and DKFZ-ZMBH Alliance
    Medical Faculty Mannheim, Heidelberg University)

  • Wolf-Karsten Hofmann

    (Medical Faculty Mannheim, Heidelberg University)

  • Carsten Müller-Tidow

    (University of Heidelberg)

  • Andreas Trumpp

    (Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH)
    Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ) and DKFZ-ZMBH Alliance
    German Cancer Consortium (DKTK))

  • Simon Haas

    (Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH)
    Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ) and DKFZ-ZMBH Alliance
    German Cancer Consortium (DKTK)
    Berlin Institute of Health (BIH))

  • Lars M. Steinmetz

    (European Molecular Biology Laboratory (EMBL), Genome Biology Unit
    Stanford University School of Medicine
    Stanford Genome Technology Center)

Abstract

Cancer stem cells drive disease progression and relapse in many types of cancer. Despite this, a thorough characterization of these cells remains elusive and with it the ability to eradicate cancer at its source. In acute myeloid leukemia (AML), leukemic stem cells (LSCs) underlie mortality but are difficult to isolate due to their low abundance and high similarity to healthy hematopoietic stem cells (HSCs). Here, we demonstrate that LSCs, HSCs, and pre-leukemic stem cells can be identified and molecularly profiled by combining single-cell transcriptomics with lineage tracing using both nuclear and mitochondrial somatic variants. While mutational status discriminates between healthy and cancerous cells, gene expression distinguishes stem cells and progenitor cell populations. Our approach enables the identification of LSC-specific gene expression programs and the characterization of differentiation blocks induced by leukemic mutations. Taken together, we demonstrate the power of single-cell multi-omic approaches in characterizing cancer stem cells.

Suggested Citation

  • Lars Velten & Benjamin A. Story & Pablo Hernández-Malmierca & Simon Raffel & Daniel R. Leonce & Jennifer Milbank & Malte Paulsen & Aykut Demir & Chelsea Szu-Tu & Robert Frömel & Christoph Lutz & Danie, 2021. "Identification of leukemic and pre-leukemic stem cells by clonal tracking from single-cell transcriptomics," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21650-1
    DOI: 10.1038/s41467-021-21650-1
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