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

Autor: Velten L; Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain. lars.velten@crg.eu.; Universitat Pompeu Fabra (UPF), Barcelona, Spain. lars.velten@crg.eu., Story BA; European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Heidelberg, Germany.; Swiss Federal Institute of Technology (ETH) Zurich, Department of Biosystems Science and Engineering, Basel, Switzerland., Hernández-Malmierca P; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany.; Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ) and DKFZ-ZMBH Alliance, Heidelberg, Germany., Raffel S; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany.; Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ) and DKFZ-ZMBH Alliance, Heidelberg, Germany.; Department of Internal Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, Heidelberg, Germany., Leonce DR; European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Heidelberg, Germany., Milbank J; European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Heidelberg, Germany., Paulsen M; European Molecular Biology Laboratory (EMBL), Flow Cytometry Core Facility, Heidelberg, Germany., Demir A; Department of Internal Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, Heidelberg, Germany., Szu-Tu C; Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain.; Universitat Pompeu Fabra (UPF), Barcelona, Spain., Frömel R; Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain.; Universitat Pompeu Fabra (UPF), Barcelona, Spain., Lutz C; Department of Internal Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, Heidelberg, Germany., Nowak D; Department of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany., Jann JC; Department of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany., Pabst C; Department of Internal Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, Heidelberg, Germany.; Molecular Medicine Partnership Unit (MMPU), University of Heidelberg and European Molecular Biology Laboratory (EMBL), Heidelberg, Germany., Boch T; Swiss Federal Institute of Technology (ETH) Zurich, Department of Biosystems Science and Engineering, Basel, Switzerland.; Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ) and DKFZ-ZMBH Alliance, Heidelberg, Germany.; Department of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany., Hofmann WK; Department of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany., Müller-Tidow C; Department of Internal Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, Heidelberg, Germany., Trumpp A; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany.; Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ) and DKFZ-ZMBH Alliance, Heidelberg, Germany.; German Cancer Consortium (DKTK), Heidelberg, Germany., Haas S; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany.; Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ) and DKFZ-ZMBH Alliance, Heidelberg, Germany.; German Cancer Consortium (DKTK), Heidelberg, Germany.; Berlin Institute of Health (BIH), Berlin, Germany.; Charité-Universitätsmedizin, Berlin, Germany.; Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany., Steinmetz LM; European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Heidelberg, Germany. larsms@embl.de.; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA. larsms@embl.de.; Stanford Genome Technology Center, Palo Alto, CA, USA. larsms@embl.de.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2021 Mar 01; Vol. 12 (1), pp. 1366. Date of Electronic Publication: 2021 Mar 01.
DOI: 10.1038/s41467-021-21650-1
Abstrakt: 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.
Databáze: MEDLINE
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