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Open AccessExperimental and spontaneous metastasis assays can result in divergence in clonal architecture
Intratumoural heterogeneity is associated with poor outcomes in breast cancer. To understand how malignant clones survive and grow in metastatic niches, in vivo models using cell lines and patient-derived xeno...
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tDCs — a distinct subset with dual functional and developmental roles
Confusion exists as to whether transitional dendritic cells are a bone fide subset or just a transitional state, as the name indicates. New data are complicating matters further by showing some interesting het...
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Mastering the use of cellular barcoding to explore cancer heterogeneity
Tumours are often composed of a multitude of malignant clones that are genomically unique, and only a few of them may have the ability to escape cancer therapy and grow as symptomatic lesions. As a result, tum...
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Non-genetic determinants of malignant clonal fitness at single-cell resolution
All cancers emerge after a period of clonal selection and subsequent clonal expansion. Although the evolutionary principles imparted by genetic intratumour heterogeneity are becoming increasingly clear1, little i...
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Spatial omics and multiplexed imaging to explore cancer biology
Understanding intratumoral heterogeneity—the molecular variation among cells within a tumor—promises to address outstanding questions in cancer biology and improve the diagnosis and treatment of specific cance...
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Single-cell analyses reveal the clonal and molecular aetiology of Flt3L-induced emergency dendritic cell development
Regulation of haematopoietic stem and progenitor cell (HSPC) fate is crucial during homeostasis and under stress conditions. Here we examine the aetiology of the Flt3 ligand (Flt3L)-mediated increase of type 1...
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A new lymphoid-primed progenitor marked by Dach1 downregulation identified with single cell multi-omics
A classical view of blood cell development is that multipotent hematopoietic stem and progenitor cells (HSPCs) become lineage-restricted at defined stages. Lin−c-Kit+Sca-1+Flt3+ cells, termed lymphoid-primed mult...
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Open AccessUnique properties of a subset of human pluripotent stem cells with high capacity for self-renewal
Archetypal human pluripotent stem cells (hPSC) are widely considered to be equivalent in developmental status to mouse epiblast stem cells, which correspond to pluripotent cells at a late post-implantation sta...
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Open AccessTargeting enhancer switching overcomes non-genetic drug resistance in acute myeloid leukaemia
Non-genetic drug resistance is increasingly recognised in various cancers. Molecular insights into this process are lacking and it is unknown whether stable non-genetic resistance can be overcome. Using single...
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Benchmarking single cell RNA-sequencing analysis pipelines using mixture control experiments
Single cell RNA-sequencing (scRNA-seq) technology has undergone rapid development in recent years, leading to an explosion in the number of tailored data analysis methods. However, the current lack of gold-sta...
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Open AccessSite-specific recombinatorics: in situ cellular barcoding with the Cre Lox system
Cellular barcoding is a recently developed biotechnology tool that enables the familial identification of progeny of individual cells in vivo. In immunology, it has been used to track the burst-sizes of multip...
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Open AccessReproducibility of Illumina platform deep sequencing errors allows accurate determination of DNA barcodes in cells
Next generation sequencing (NGS) of amplified DNA is a powerful tool to describe genetic heterogeneity within cell populations that can both be used to investigate the clonal structure of cell populations and ...
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Article
Dendritic cells, monocytes and macrophages: a unified nomenclature based on ontogeny
Cells of the mononuclear phagocyte system (MPS) are usually defined by particular functional or phenotypical characteristics. However, this has led to confusion in the field, as many of the criteria that are u...
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Diverse and heritable lineage imprinting of early haematopoietic progenitors
In vivo ‘cellular barcoding’ shows that early haematopoietic progenitors are heterogeneous in the cell types that they produce, and this is partly due to an ‘imprinting’ of fate in progenitors, including for a se...
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Protocol
CD8+, CD8−, and Plasmacytoid Dendritic Cell Generation In Vitro Using flt3 Ligand
The generation of dendritic cells (DCs) from monocytes and early progenitors in GM-CSF cultures has been the gold standard for in vitro generation of DCs for three decades. However, the most recent evidence su...
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Protocol
Generation of Large Numbers of Pro-DCs and Pre-DCs In Vitro
The CD8+, CD8−, and plasmacytoid dendritic cell (DC) subtypes develop from progenitors that express surface fms-like tyrosine kinase 3 (Flt3). Recently, two developmentally sequential progenitors have been identi...
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Development of plasmacytoid and conventional dendritic cell subtypes from single precursor cells derived in vitro and in vivo
The development of functionally specialized subtypes of dendritic cells (DCs) can be modeled through the culture of bone marrow with the ligand for the cytokine receptor Flt3. Such cultures produce DCs resembl...
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Article
Steady-state and inflammatory dendritic-cell development
The functionally specialized subtypes of dendritic cells (DCs) are the products of different branches or sub-branches of haematopoietic pathways, which involve...
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Intrasplenic steady-state dendritic cell precursors that are distinct from monocytes
Immediate precursors of the many subtypes of dendritic cells (DCs) remain obscure. Here we purified a splenic precursor population that produced all splenic CD8+ and CD8− conventional DCs (cDCs) but not plasmacyt...
