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

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, Daniel Nowak, Johann-Christoph Jann, Caroline Pabst, Tobias Boch, Wolf-Karsten Hofmann, Carsten Müller-Tidow, Andreas Trumpp, Simon Haas and Lars M. Steinmetz ()
Additional contact information
Lars Velten: Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology
Benjamin A. Story: European Molecular Biology Laboratory (EMBL), Genome Biology Unit
Pablo Hernández-Malmierca: Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH)
Simon Raffel: Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH)
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
Robert Frömel: Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology
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
Tobias Boch: Swiss Federal Institute of Technology (ETH) Zurich, Department of Biosystems Science and Engineering
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)
Simon Haas: Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH)
Lars M. Steinmetz: European Molecular Biology Laboratory (EMBL), Genome Biology Unit

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21650-1

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DOI: 10.1038/s41467-021-21650-1

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