scholarly journals Modeling non-genetic dynamics of cancer cell states measured by single-cell analysis: Uncovering bifurcations that explain why treatment either kills a cancer cell or makes it resistant

2019 ◽  
Author(s):  
S. Huang
Keyword(s):  
Dynamical System ◽  
Single Cell ◽  
Cancer Cell ◽  
Single Cell Analysis ◽  
Cell Plasticity ◽  
System A ◽  
Critical Transitions ◽  
Stable Attractor ◽  
Statistical Ensembles ◽  
Tumor Cell Plasticity

AbstractSingle-cell transcriptomics offers a new vista on non-genetic tumor cell plasticity, a neglected aspect of cancer. The gene expression state of each cell is governed by the gene regulatory network which represents a high-dimensional non-linear dynamical system that generates multiple stable attractor states and undergoes destabilizing bifurcations, manifest as critical transitions. Modeling clonal cell population as statistical ensembles of the same dynamical system, a index IC is derived for detecting destabilization towards critical transitions in single-cell molecular profiles. Therapy-induced bifurcation explains why treatment backfires: a drug-treated cell is imposed the binary choice to either apoptose or become a cancer-stem cell.

scholarly journals Application of Single-Cell Multi-Omics in Dissecting Cancer Cell Plasticity and Tumor Heterogeneity

2021 ◽  
Vol 8 ◽  
Author(s):  
Deshen Pan ◽  
Deshui Jia
Keyword(s):  
Single Cell ◽  
Cancer Cell ◽  
Tumor Heterogeneity ◽  
Recent Progress ◽  
Molecular Mechanisms ◽  
High Throughput Sequencing ◽  
Tumor Development ◽  
Cell Plasticity ◽  
Translational Cancer Research ◽  
Cellular Components

Tumor heterogeneity, a hallmark of cancer, impairs the efficacy of cancer therapy and drives tumor progression. Exploring inter- and intra-tumoral heterogeneity not only provides insights into tumor development and progression, but also guides the design of personalized therapies. Previously, high-throughput sequencing techniques have been used to investigate the heterogeneity of tumor ecosystems. However, they could not provide a high-resolution landscape of cellular components in tumor ecosystem. Recently, advance in single-cell technologies has provided an unprecedented resolution to uncover the intra-tumoral heterogeneity by profiling the transcriptomes, genomes, proteomes and epigenomes of the cellular components and also their spatial distribution, which greatly accelerated the process of basic and translational cancer research. Importantly, it has been demonstrated that some cancer cells are able to transit between different states in order to adapt to the changing tumor microenvironment, which led to increased cellular plasticity and tumor heterogeneity. Understanding the molecular mechanisms driving cancer cell plasticity is critical for developing precision therapies. In this review, we summarize the recent progress in dissecting the cancer cell plasticity and tumor heterogeneity by use of single-cell multi-omics techniques.

scholarly journals Author Correction: Single-cell analysis of EphA clustering phenotypes to probe cancer cell heterogeneity

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Andrea Ravasio ◽  
Myint Z. Myaing ◽  
Shumei Chia ◽  
Aditya Arora ◽  
Aneesh Sathe ◽  
...  
Keyword(s):  
Single Cell ◽  
Cancer Cell ◽  
Single Cell Analysis ◽  
Cell Analysis ◽  
Cell Heterogeneity

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

scholarly journals Author Correction: Single-cell analysis of EphA clustering phenotypes to probe cancer cell heterogeneity

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Andrea Ravasio ◽  
Myint Z. Myaing ◽  
Shumei Chia ◽  
Aditya Arora ◽  
Aneesh Sathe ◽  
...  
Keyword(s):  
Single Cell ◽  
Cancer Cell ◽  
Single Cell Analysis ◽  
Cell Analysis ◽  
Cell Heterogeneity

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

scholarly journals Single-cell analysis of EphA clustering phenotypes to probe cancer cell heterogeneity

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Andrea Ravasio ◽  
Myint Z. Myaing ◽  
Shumei Chia ◽  
Aditya Arora ◽  
Aneesh Sathe ◽  
...  
Keyword(s):  
Single Cell ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Tyrosine Kinases ◽  
Spatial Organization ◽  
Single Cell Analysis ◽  
Cell Populations ◽  
Effective Manner ◽  
Migration Potential

AbstractThe Eph family of receptor tyrosine kinases is crucial for assembly and maintenance of healthy tissues. Dysfunction in Eph signaling is causally associated with cancer progression. In breast cancer cells, dysregulated Eph signaling has been linked to alterations in receptor clustering abilities. Here, we implemented a single-cell assay and a scoring scheme to systematically probe the spatial organization of activated EphA receptors in multiple carcinoma cells. We show that cancer cells retain EphA clustering phenotype over several generations, and the degree of clustering reported for migration potential both at population and single-cell levels. Finally, using patient-derived cancer lines, we probed the evolution of EphA signalling in cell populations that underwent metastatic transformation and acquisition of drug resistance. Taken together, our scalable approach provides a reliable scoring scheme for EphA clustering that is consistent over multiple carcinomas and can assay heterogeneity of cancer cell populations in a cost- and time-effective manner.

scholarly journals Single-cell analysis of EphA clustering phenotypes to probe cancer cell heterogeneity

2019 ◽  
Author(s):  
Andrea Ravasio ◽  
Myint Zu Myaing ◽  
Shumei Chia ◽  
Aditya Arora ◽  
Aneesh Sathe ◽  
...  
Keyword(s):  
Single Cell ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Tyrosine Kinases ◽  
Spatial Organization ◽  
Single Cell Analysis ◽  
Cell Populations ◽  
Eph Receptors ◽  
Effective Manner

Abstract Eph receptors, a family of receptor tyrosine kinases, play a crutial role in the assembly and maintenance of healthy tissues. Dysfunction in Eph signaling are causally and correlatively associated with cancer progression. In breast cancer cells, dysregulated Eph signaling has been largely linked to alterations in receptor clustering abilities. In the present study, we implemented a single-cell assay and a scoring scheme to systematically probe the spatial organization of activated EphA receptor in carcinoma cells of different origin. Using this assay, we found that cancer cells retained EphA clustering phenotype upon cell division for several generations and degree of clustering reported for population as well as single-cell migration potential. Finally, using patient-derived cancer cell lines, we probed the evolution of EphA signalling in cancer cell populations that underwent metastatic transformation and acquisition of drug resistance. Taken together, our simple and scalable approach provides a reliable quantitation of EphA associated gene expression and phenotypes in multiple carcinomas and can assay the heterogeneity of cancer cell populations in a cost- and time-effective manner.

scholarly journals Micromagnetic Cancer Cell Immobilization and Release for Real-Time Single Cell Analysis

2017 ◽  
Vol 427 ◽  
pp. 7-13 ◽  
Author(s):  
Devina Jaiswal ◽  
Armin Tahmasbi Rad ◽  
Mu-Ping Nieh ◽  
Kevin P. Claffey ◽  
Kazunori Hoshino
Keyword(s):  
Single Cell ◽  
Real Time ◽  
Cancer Cell ◽  
Single Cell Analysis ◽  
Cell Immobilization ◽  
Cell Analysis
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