scholarly journals Lineage tracing of Notch1-expressing cells in intestinal tumours reveals a distinct population of cancer stem cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Larissa Mourao ◽  
Guillaume Jacquemin ◽  
Mathilde Huyghe ◽  
Wojciech J. Nawrocki ◽  
Naoual Menssouri ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Lineage Tracing ◽  
Distinct Population

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

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Lars Velten ◽  
Benjamin A. Story ◽  
Pablo Hernández-Malmierca ◽  
Simon Raffel ◽  
Daniel R. Leonce ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Single Cell ◽  
Lineage Tracing ◽  
Specific Gene ◽  
Leukemic Stem Cells ◽  
Hematopoietic Stem ◽  
Mutational Status

AbstractCancer 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.

scholarly journals Heritable tumor cell division rate heterogeneity induces clonal dominance

2017 ◽  
Author(s):  
Margriet M. Palm ◽  
Marjet Elemans ◽  
Joost B. Beltman
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Lineage Tracing ◽  
Hierarchical Organization ◽  
Rate Heterogeneity ◽  
Division Rate ◽  
Cell Division Rate ◽  
Mutational Processes ◽  
Selection Of

AbstractTumors consist of a hierarchical population of cells that differ in their phenotype and genotype. This hierarchical organization of cells means that a few clones (i.e., cells and several generations of offspring) are abundant while most are rare, which is called clonal dominance. Such dominance also occurred in published in vitro iterated growth and passage experiments with tumor cells in which genetic barcodes were used for lineage tracing. A potential source for such heterogeneity is that dominant clones derive from cancer stem cells with an unlimited self-renewal capacity. Furthermore, ongoing evolution within the growing population may also induce clonal dominance. To understand how clonal dominance developed in the iterated growth and passage experiments, we built a computational model that accurately simulates these experiments. The model simulations reproduced the clonal dominance that developed in in vitro iterated growth and passage experiments when the division rates vary between cells, due to a combination of initial variation and of ongoing mutational processes. In contrast, the experimental results can neither be reproduced with a model that considers random growth and passage, nor with a model based on cancer stem cells. Altogether, our model suggests that in vitro clonal dominance develops due to selection of fast-dividing clones.

scholarly journals Identification of a distinct population of CD133+CXCR4+ cancer stem cells in ovarian cancer

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Michele Cioffi ◽  
Crescenzo D’Alterio ◽  
Rosalba Camerlingo ◽  
Virginia Tirino ◽  
Claudia Consales ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Distinct Population

scholarly journals Breast Cancer Stem Cells: Biomarkers, Identification and Isolation Methods, Regulating Mechanisms, Cellular Origin, and Beyond

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3765
Author(s):  
Xiaoli Zhang ◽  
Kimerly Powell ◽  
Lang Li
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Current Knowledge ◽  
Cell Lineage ◽  
Lineage Tracing ◽  
Breast Cancer Stem Cells ◽  
Full Spectrum ◽  
Cellular Origin ◽  
Treatment Responses

Despite recent advances in diagnosis and treatment, breast cancer (BC) is still a major cause of cancer-related mortality in women. Breast cancer stem cells (BCSCs) are a small but significant subpopulation of heterogeneous breast cancer cells demonstrating strong self-renewal and proliferation properties. Accumulating evidence has proved that BCSCs are the driving force behind BC tumor initiation, progression, metastasis, drug resistance, and recurrence. As a heterogeneous disease, BC contains a full spectrum of different BC subtypes, and different subtypes of BC further exhibit distinct subtypes and proportions of BCSCs, which correspond to different treatment responses and disease-specific outcomes. This review summarized the current knowledge of BCSC biomarkers and their clinical relevance, the methods for the identification and isolation of BCSCs, and the mechanisms regulating BCSCs. We also discussed the cellular origin of BCSCs and the current advances in single-cell lineage tracing and transcriptomics and their potential in identifying the origin and lineage development of BCSCs.

scholarly journals Lineage tracing of Notch1-expressing cells in intestinal tumours reveals a distinct population of cancer stem cells

2018 ◽  
Author(s):  
Larissa Mourao ◽  
Guillaume Jacquemin ◽  
Mathilde Huyghe ◽  
Wojciech J. Nawrocki ◽  
Naoual Menssouri ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Critical Role ◽  
Tumour Cells ◽  
Lineage Tracing ◽  
Intestinal Stem Cells ◽  
Cellular Targets ◽  
Transcriptional Signature ◽  
Stem Cell Populations ◽  
Notch1 Receptor

AbstractColon tumours are hierarchically organized and contain multipotent self-renewing cells, called Cancer Stem Cells (CSCs). We have previously shown that the Notch1 receptor is expressed in Intestinal Stem Cells (ISCs); given the critical role played by Notch signalling in promoting intestinal tumourigenesis, we explored Notch1 expression in tumours. Combining lineage tracing in two tumour models with transcriptomic analyses, we found that Notch1 + tumour cells are undifferentiated, proliferative and capable of indefinite self-renewal and of generating a heterogeneous clonal progeny. Molecularly, the transcriptional signature of Notch1+ tumour cells highly correlates with ISCs, suggestive of their origin from normal crypt cells. Surprisingly, Notch1+ expression labels a subset of CSCs that show reduced levels of Lgr5, a reported CSCs marker. The existence of distinct stem cell populations within intestinal tumours highlights the necessity of better understanding their hierarchy and behaviour, to identify the correct cellular targets for therapy.

scholarly journals Therapeutic Targeting Strategies of Cancer Stem Cells in Gastrointestinal Malignancies

Biomedicines ◽  
2019 ◽  
Vol 7 (1) ◽  
pp. 17 ◽  
Author(s):  
Mohamad Sonbol ◽  
Daniel Ahn ◽  
Tanios Bekaii-Saab
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Treatment Strategies ◽  
Treatment Resistance ◽  
Cancer Growth ◽  
Distinct Population ◽  
Therapeutic Targeting ◽  
Gastrointestinal Malignancies ◽  
Novel Treatment ◽  
Novel Treatment Strategies

Cancer stem cells (CSCs) are thought to be a distinct population of cells within a tumor mass that are capable of asymmetric division and known to have chemoresistant characteristics. The description and identification of CSC models in cancer growth and recurrence has inspired the design of novel treatment strategies to overcome treatment resistance by targeting both CSCs and non-CSC tumor cells. Several cellular signaling pathways have been described as playing a role in the induction and maintenance of stemness in CSCs, such as the Wnt/β-catenin, Notch, STAT3, and Hedgehog pathways. In this review, we aim to review some of the ongoing CSC therapeutic targeting strategies in gastrointestinal malignancies.

scholarly journals Novel Strategy for Lineage Tracing of Cancer Stem Cells

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Tuan Minh Nguyen ◽  
Edmund C. Chang ◽  
Jeffrey M. Rosen
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Lineage Tracing ◽  
Novel Strategy
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