Abstract LB-119: Single-cell live imaging of paclitaxel-resistant cancer cell generation

2016 ◽  
Author(s):  
Na Niu ◽  
Jie Zhang ◽  
Ning Zhang ◽  
Imelda Mercado-Uribe ◽  
Fangfang Tao ◽  
...  
Keyword(s):  
Single Cell ◽  
Cancer Cell ◽  
Live Imaging ◽  
Cell Generation

scholarly journals Tumor to normal single-cell mRNA comparisons reveal a pan-neuroblastoma cancer cell

2021 ◽  
Vol 7 (6) ◽  
pp. eabd3311
Author(s):  
Gerda Kildisiute ◽  
Waleed M. Kholosy ◽  
Matthew D. Young ◽  
Kenny Roberts ◽  
Rasa Elmentaite ◽  
...  
Keyword(s):  
Childhood Cancer ◽  
Single Cell ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Developmental Stages ◽  
Neuroblastoma Cells ◽  
Cell Type ◽  
Adrenal Cell ◽  
Universal Feature ◽  
Principal Finding

Neuroblastoma is a childhood cancer that resembles developmental stages of the neural crest. It is not established what developmental processes neuroblastoma cancer cells represent. Here, we sought to reveal the phenotype of neuroblastoma cancer cells by comparing cancer (n = 19,723) with normal fetal adrenal single-cell transcriptomes (n = 57,972). Our principal finding was that the neuroblastoma cancer cell resembled fetal sympathoblasts, but no other fetal adrenal cell type. The sympathoblastic state was a universal feature of neuroblastoma cells, transcending cell cluster diversity, individual patients, and clinical phenotypes. We substantiated our findings in 650 neuroblastoma bulk transcriptomes and by integrating canonical features of the neuroblastoma genome with transcriptional signals. Overall, our observations indicate that a pan-neuroblastoma cancer cell state exists, which may be attractive for novel immunotherapeutic and targeted avenues.

scholarly journals Quantitative single-cell live imaging links HES5 dynamics with cell-state and fate in murine neurogenesis

2018 ◽  
Author(s):  
Cerys S Manning ◽  
Veronica Biga ◽  
James Boyd ◽  
Jochen Kursawe ◽  
Bodvar Ymisson ◽  
...  
Keyword(s):  
Single Cell ◽  
Cell Fate ◽  
Live Imaging ◽  
Protein Quantification ◽  
Expression Change ◽  
Dynamic View ◽  
Transient Period ◽  
Gene Expression Dynamics ◽  
Transcription Factor Expression ◽  
Protein Fluctuations

AbstractDuring embryogenesis cells make fate decisions within complex tissue environments. The levels and dynamics of transcription factor expression regulate these decisions. Here we use single cell live imaging of an endogenous HES5 reporter and absolute protein quantification to gain a dynamic view of neurogenesis in the embryonic mammalian spinal cord. We report that dividing neural progenitors show both aperiodic and periodic HES5 protein fluctuations. Mathematical modelling suggests that in progenitor cells the HES5 oscillator operates close to its bifurcation boundary where stochastic conversions between dynamics are possible. HES5 expression becomes more frequently periodic as cells transition to differentiation which, coupled with an overall decline in HES5 expression, creates a transient period of oscillations with higher fold expression change. This increases the decoding capacity of HES5 oscillations and correlates with interneuron versus motor neuron cell fate. Thus, HES5 undergoes complex changes in gene expression dynamics as cells differentiate.

scholarly journals Metabolic Reprogramming from Glycolysis to Fatty Acid Uptake and beta-Oxidation in Platinum-Resistant Cancer Cells

2021 ◽  
Author(s):  
Junjie Li ◽  
Yuying Tan ◽  
Guangyuan Zhao ◽  
Kai-Chih Huang ◽  
Horacio Cardenas ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Fatty Acid ◽  
Single Cell ◽  
Cancer Cell ◽  
Aerobic Glycolysis ◽  
Fatty Acid Uptake ◽  
Metabolic Reprogramming ◽  
De Novo Lipogenesis ◽  
Acid Uptake ◽  
Beta Oxidation

Increased aerobic glycolysis is widely considered as a hallmark of cancer. Yet, cancer cell metabolic reprograming during development of therapeutic resistance is under-studied. Here, through high-throughput stimulated Raman scattering imaging and single cell analysis, we found that cisplatin-resistant cells exhibit increased uptake of exogenous fatty acids, accompanied with decreased glucose uptake and de novo lipogenesis, indicating a reprogramming from glucose and glycolysis dependent to fatty acid uptake and beta-oxidation dependent anabolic and energy metabolism. A metabolic index incorporating measurements of glucose derived anabolism and fatty acid uptake correlates linearly to the level of resistance to cisplatin in ovarian cancer cell lines and in primary cells isolated from ovarian cancer patients. Mechanistically, the increased fatty acid uptake facilitates cancer cell survival under cisplatin-induced oxidative stress by enhancing energy production through beta-oxidation. Consequently, blocking fatty acid beta-oxidation by a small molecule inhibitor in combination with cisplatin or carboplatin synergistically suppressed ovarian cancer proliferation in vitro and growth of patient-derived xenograft in vivo. Collectively, these findings support a new way for rapid detection of cisplatin-resistance at single cell level and a new strategy for treatment of cisplatin-resistant tumors.

Predicting cancer cell invasion by single-cell physical phenotyping

2018 ◽  
Vol 10 (4) ◽  
pp. 218-231 ◽  
Author(s):  
Kendra D. Nyberg ◽  
Samuel L. Bruce ◽  
Angelyn V. Nguyen ◽  
Clara K. Chan ◽  
Navjot K. Gill ◽  
...  
Keyword(s):  
Single Cell ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Cancer Cell Invasion

scholarly journals Joint single cell DNA-seq and RNA-seq of gastric cancer cell lines reveals rules of in vitro evolution

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Noemi Andor ◽  
Billy T Lau ◽  
Claudia Catalanotti ◽  
Anuja Sathe ◽  
Matthew Kubit ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Single Cell ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Gastric Cancer Cell ◽  
Phenotypic Diversity ◽  
Single Cells ◽  
Cancer Cell Lines ◽  
Gastric Cancer Cell Lines

Abstract Cancer cell lines are not homogeneous nor are they static in their genetic state and biological properties. Genetic, transcriptional and phenotypic diversity within cell lines contributes to the lack of experimental reproducibility frequently observed in tissue-culture-based studies. While cancer cell line heterogeneity has been generally recognized, there are no studies which quantify the number of clones that coexist within cell lines and their distinguishing characteristics. We used a single-cell DNA sequencing approach to characterize the cellular diversity within nine gastric cancer cell lines and integrated this information with single-cell RNA sequencing. Overall, we sequenced the genomes of 8824 cells, identifying between 2 and 12 clones per cell line. Using the transcriptomes of more than 28 000 single cells from the same cell lines, we independently corroborated 88% of the clonal structure determined from single cell DNA analysis. For one of these cell lines, we identified cell surface markers that distinguished two subpopulations and used flow cytometry to sort these two clones. We identified substantial proportions of replicating cells in each cell line, assigned these cells to subclones detected among the G0/G1 population and used the proportion of replicating cells per subclone as a surrogate of each subclone's growth rate.

scholarly journals Single Cell Hydrodynamic Stretching and Microsieve Filtration Reveal Genetic, Phenotypic and Treatment-Related Links to Cellular Deformability

Micromachines ◽  
2020 ◽  
Vol 11 (5) ◽  
pp. 486
Author(s):  
Fenfang Li ◽  
Igor Cima ◽  
Jess Honganh Vo ◽  
Min-Han Tan ◽  
Claus Dieter Ohl
Keyword(s):  
Single Cell ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Cancer Metastasis ◽  
Extensional Flow ◽  
Colorectal Cancer Cell Line ◽  
Mesenchymal Transition ◽  
Cellular Models ◽  
Cellular Deformability

Deformability is shown to correlate with the invasiveness and metastasis of cancer cells. Recent studies suggest epithelial-to-mesenchymal transition (EMT) might enable cancer metastasis. However, the correlation of EMT with cancer cell deformability has not been well elucidated. Cellular deformability could also help evaluate the drug response of cancer cells. Here, we combine hydrodynamic stretching and microsieve filtration to study cellular deformability in several cellular models. Hydrodynamic stretching uses extensional flow to rapidly quantify cellular deformability and size with high throughput at the single cell level. Microsieve filtration can rapidly estimate relative deformability in cellular populations. We show that colorectal cancer cell line RKO with the mesenchymal-like feature is more flexible than the epithelial-like HCT116. In another model, the breast epithelial cells MCF10A with deletion of the TP53 gene are also significantly more deformable compared to their isogenic wildtype counterpart, indicating a potential genetic link to cellular deformability. We also find that the drug docetaxel leads to an increase in the size of A549 lung cancer cells. The ability to associate mechanical properties of cancer cells with their phenotypes and genetics using single cell hydrodynamic stretching or the microsieve may help to deepen our understanding of the basic properties of cancer progression.

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