Metastasis

Cell, Journal Year: 2023, Volume and Issue: 186(8), P. 1564 - 1579

Published: April 1, 2023

Language: Английский

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Applications of single-cell sequencing in cancer research: progress and perspectives

Journal of Hematology & Oncology, Journal Year: 2021, Volume and Issue: 14(1)

Published: June 9, 2021

Single-cell sequencing, including genomics, transcriptomics, epigenomics, proteomics and metabolomics is a powerful tool to decipher the cellular molecular landscape at single-cell resolution, unlike bulk which provides averaged data. The use of sequencing in cancer research has revolutionized our understanding biological characteristics dynamics within lesions. In this review, we summarize emerging technologies recent progress obtained by information related landscapes malignant cells immune cells, tumor heterogeneity, circulating underlying mechanisms behaviors. Overall, prospects facilitating diagnosis, targeted therapy prognostic prediction among spectrum tumors are bright. near future, advances will undoubtedly improve highlight potential precise therapeutic targets for patients.

Language: Английский

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CRISPR in cancer biology and therapy

Nature reviews. Cancer, Journal Year: 2022, Volume and Issue: 22(5), P. 259 - 279

Published: Feb. 22, 2022

Language: Английский

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Single-cell lineage tracing of metastatic cancer reveals selection of hybrid EMT states

Cancer Cell, Journal Year: 2021, Volume and Issue: 39(8), P. 1150 - 1162.e9

Published: June 10, 2021

Language: Английский

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Single-cell lineages reveal the rates, routes, and drivers of metastasis in cancer xenografts

Science, Journal Year: 2021, Volume and Issue: 371(6532)

Published: Jan. 21, 2021

Following cancer through the body The heterogeneity of mammalian tumors has been well documented, but it remains unknown how differences between individual cells lead to metastasis and spread throughout body. Quinn et al. created a Cas9-based lineage tracer used single-cell sequencing generate phylogenies follow movement metastatic human implanted in lung mouse xenograph model. Using this model, they found that within same cell line, exhibited diverse phenotypes. These subclones differential gene expression profiles, some which were previously associated with metastasis. Science , issue p. eabc1944

Language: Английский

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Lineage tracing reveals the phylodynamics, plasticity, and paths of tumor evolution

Cell, Journal Year: 2022, Volume and Issue: 185(11), P. 1905 - 1923.e25

Published: May 1, 2022

Tumor evolution is driven by the progressive acquisition of genetic and epigenetic alterations that enable uncontrolled growth expansion to neighboring distal tissues. The study phylogenetic relationships between cancer cells provides key insights into these processes. Here, we introduced an evolving lineage-tracing system with a single-cell RNA-seq readout mouse model Kras;Trp53(KP)-driven lung adenocarcinoma tracked tumor from single-transformed metastatic tumors at unprecedented resolution. We found loss initial, stable alveolar-type2-like state was accompanied transient increase in plasticity. This followed adoption distinct transcriptional programs rapid and, ultimately, clonal sweep subclones capable metastasizing. Finally, develop through stereotypical evolutionary trajectories, perturbing additional suppressors accelerates progression creating novel trajectories. Our elucidates hierarchical nature more broadly, enables in-depth studies progression.

Language: Английский

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Applications of single-cell RNA sequencing in drug discovery and development

Nature Reviews Drug Discovery, Journal Year: 2023, Volume and Issue: 22(6), P. 496 - 520

Published: April 28, 2023

Single-cell technologies, particularly single-cell RNA sequencing (scRNA-seq) methods, together with associated computational tools and the growing availability of public data resources, are transforming drug discovery development. New opportunities emerging in target identification owing to improved disease understanding through cell subtyping, highly multiplexed functional genomics screens incorporating scRNA-seq enhancing credentialling prioritization. ScRNA-seq is also aiding selection relevant preclinical models providing new insights into mechanisms action. In clinical development, can inform decision-making via biomarker for patient stratification more precise monitoring response progression. Here, we illustrate how methods being applied key steps discuss ongoing challenges their implementation pharmaceutical industry. There have been significant recent advances development remarkable Ferran colleagues primarily pipeline, from decision-making. Ongoing potential future directions discussed.

Language: Английский

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A new era in functional genomics screens

Nature Reviews Genetics, Journal Year: 2021, Volume and Issue: 23(2), P. 89 - 103

Published: Sept. 20, 2021

Language: Английский

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Lineage recording in human cerebral organoids

Nature Methods, Journal Year: 2021, Volume and Issue: 19(1), P. 90 - 99

Published: Dec. 30, 2021

Abstract Induced pluripotent stem cell (iPSC)-derived organoids provide models to study human organ development. Single-cell transcriptomics enable highly resolved descriptions of states within these systems; however, approaches are needed directly measure lineage relationships. Here we establish iTracer, a recorder that combines reporter barcodes with inducible CRISPR–Cas9 scarring and is compatible single-cell spatial transcriptomics. We apply iTracer explore clonality dynamics during cerebral organoid development identify time window fate restriction as well variation in neurogenic between progenitor neuron families. also long-term four-dimensional light-sheet microscopy for recording confirm regional the developing neuroepithelium. incorporate gene perturbation (iTracer-perturb) assess effect mosaic TSC2 mutations on Our data shed light how lineages fates established formation. More broadly, our techniques can be adapted any iPSC-derived culture system dissect alterations normal or perturbed

Language: Английский

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Variability within rare cell states enables multiple paths toward drug resistance

Nature Biotechnology, Journal Year: 2021, Volume and Issue: 39(7), P. 865 - 876

Published: Feb. 22, 2021

Language: Английский

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