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Identification of leukemic and pre-leukemic stem cells by clonal tracking from single-cell transcriptomics
by
Lutz, Christoph
, Hernández-Malmierca, Pablo
, Hofmann, Wolf-Karsten
, Story, Benjamin A.
, Milbank, Jennifer
, Demir, Aykut
, Velten, Lars
, Leonce, Daniel R.
, Nowak, Daniel
, Müller-Tidow, Carsten
, Steinmetz, Lars M.
, Trumpp, Andreas
, Pabst, Caroline
, Raffel, Simon
, Paulsen, Malte
, Jann, Johann-Christoph
, Boch, Tobias
, Haas, Simon
, Szu-Tu, Chelsea
, Frömel, Robert
in
38/39
/ 38/91
/ 45/100
/ 631/250/232
/ 631/61/212/2019
/ 631/67/1990/283/1897
/ 631/67/2329
/ 631/67/71
/ Acute myeloid leukemia
/ Biomarkers, Tumor - genetics
/ Bone Marrow - pathology
/ Cancer
/ Cell Differentiation
/ Clone Cells - pathology
/ Gene expression
/ Gene Expression Regulation, Leukemic
/ Genome
/ Hematopoietic stem cells
/ Hematopoietic Stem Cells - pathology
/ Humanities and Social Sciences
/ Humans
/ K562 Cells
/ Leukemia
/ Leukemia, Myeloid, Acute - genetics
/ Leukemia, Myeloid, Acute - pathology
/ Mitochondria
/ Mitochondria - genetics
/ multidisciplinary
/ Mutation
/ Mutation - genetics
/ Myeloid leukemia
/ Neoplastic Stem Cells - metabolism
/ Neoplastic Stem Cells - pathology
/ Progenitor cells
/ Quorum sensing
/ Science
/ Science (multidisciplinary)
/ Single-Cell Analysis
/ Stem cells
/ Tracking
/ Transcriptome - genetics
2021
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Identification of leukemic and pre-leukemic stem cells by clonal tracking from single-cell transcriptomics
by
Lutz, Christoph
, Hernández-Malmierca, Pablo
, Hofmann, Wolf-Karsten
, Story, Benjamin A.
, Milbank, Jennifer
, Demir, Aykut
, Velten, Lars
, Leonce, Daniel R.
, Nowak, Daniel
, Müller-Tidow, Carsten
, Steinmetz, Lars M.
, Trumpp, Andreas
, Pabst, Caroline
, Raffel, Simon
, Paulsen, Malte
, Jann, Johann-Christoph
, Boch, Tobias
, Haas, Simon
, Szu-Tu, Chelsea
, Frömel, Robert
in
38/39
/ 38/91
/ 45/100
/ 631/250/232
/ 631/61/212/2019
/ 631/67/1990/283/1897
/ 631/67/2329
/ 631/67/71
/ Acute myeloid leukemia
/ Biomarkers, Tumor - genetics
/ Bone Marrow - pathology
/ Cancer
/ Cell Differentiation
/ Clone Cells - pathology
/ Gene expression
/ Gene Expression Regulation, Leukemic
/ Genome
/ Hematopoietic stem cells
/ Hematopoietic Stem Cells - pathology
/ Humanities and Social Sciences
/ Humans
/ K562 Cells
/ Leukemia
/ Leukemia, Myeloid, Acute - genetics
/ Leukemia, Myeloid, Acute - pathology
/ Mitochondria
/ Mitochondria - genetics
/ multidisciplinary
/ Mutation
/ Mutation - genetics
/ Myeloid leukemia
/ Neoplastic Stem Cells - metabolism
/ Neoplastic Stem Cells - pathology
/ Progenitor cells
/ Quorum sensing
/ Science
/ Science (multidisciplinary)
/ Single-Cell Analysis
/ Stem cells
/ Tracking
/ Transcriptome - genetics
2021
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Identification of leukemic and pre-leukemic stem cells by clonal tracking from single-cell transcriptomics
by
Lutz, Christoph
, Hernández-Malmierca, Pablo
, Hofmann, Wolf-Karsten
, Story, Benjamin A.
, Milbank, Jennifer
, Demir, Aykut
, Velten, Lars
, Leonce, Daniel R.
, Nowak, Daniel
, Müller-Tidow, Carsten
, Steinmetz, Lars M.
, Trumpp, Andreas
, Pabst, Caroline
, Raffel, Simon
, Paulsen, Malte
, Jann, Johann-Christoph
, Boch, Tobias
, Haas, Simon
, Szu-Tu, Chelsea
, Frömel, Robert
in
38/39
/ 38/91
/ 45/100
/ 631/250/232
/ 631/61/212/2019
/ 631/67/1990/283/1897
/ 631/67/2329
/ 631/67/71
/ Acute myeloid leukemia
/ Biomarkers, Tumor - genetics
/ Bone Marrow - pathology
/ Cancer
/ Cell Differentiation
/ Clone Cells - pathology
/ Gene expression
/ Gene Expression Regulation, Leukemic
/ Genome
/ Hematopoietic stem cells
/ Hematopoietic Stem Cells - pathology
/ Humanities and Social Sciences
/ Humans
/ K562 Cells
/ Leukemia
/ Leukemia, Myeloid, Acute - genetics
/ Leukemia, Myeloid, Acute - pathology
/ Mitochondria
/ Mitochondria - genetics
/ multidisciplinary
/ Mutation
/ Mutation - genetics
/ Myeloid leukemia
/ Neoplastic Stem Cells - metabolism
/ Neoplastic Stem Cells - pathology
/ Progenitor cells
/ Quorum sensing
/ Science
/ Science (multidisciplinary)
/ Single-Cell Analysis
/ Stem cells
/ Tracking
/ Transcriptome - genetics
2021
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Identification of leukemic and pre-leukemic stem cells by clonal tracking from single-cell transcriptomics
Journal Article
Identification of leukemic and pre-leukemic stem cells by clonal tracking from single-cell transcriptomics
2021
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Overview
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.
Leukaemic stem cells drive acute myeloid leukaemia (AML) progression and relapse but they are incompletely characterized. Here, the authors combine single-cell transcriptomics and clonal tracking using nuclear and mitochondrial somatic variants to distinguish healthy, pre-leukaemic and leukaemic stem cells in AML.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 38/91
/ 45/100
/ Biomarkers, Tumor - genetics
/ Cancer
/ Gene Expression Regulation, Leukemic
/ Genome
/ Hematopoietic Stem Cells - pathology
/ Humanities and Social Sciences
/ Humans
/ Leukemia
/ Leukemia, Myeloid, Acute - genetics
/ Leukemia, Myeloid, Acute - pathology
/ Mutation
/ Neoplastic Stem Cells - metabolism
/ Neoplastic Stem Cells - pathology
/ Science
/ Tracking
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