Using Single-Cell Amperometry and Intracellular Vesicle Impact Electrochemical Cytometry To Shed Light on the Biphasic Effects of Lidocaine on Exocytosis

2018 ◽  
Vol 9 (12) ◽  
pp. 2941-2947 ◽  
Author(s):  
Daixin Ye ◽  
Chaoyi Gu ◽  
Andrew Ewing
Keyword(s):  
Single Cell ◽  
Intracellular Vesicle ◽  
Shed Light ◽  
Electrochemical Cytometry

scholarly journals A Roadmap to Immunotherapy: Lesson from the Hallmarks and Signaling Pathways of Cancer

2020 ◽  
Author(s):  
Afshin Derakhshani ◽  
Zeinab Rostami ◽  
Hossein Safarpour ◽  
Sina Taefehshokr ◽  
Neda Jalili Tabrizi ◽  
...  
Keyword(s):  
Single Cell ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Current Knowledge ◽  
Expression Patterns ◽  
Therapeutic Approaches ◽  
The Road ◽  
Profiling Techniques ◽  
Novel Biomarkers ◽  
Shed Light

Cancer is the second leading cause of death worldwide. It is theorized that underlying genetic and epigenetic changes enable cells to proliferate out of control by escaping regulatory mechanisms. Although traditional molecular profiling techniques, i.e., bulk sequencing, can identify common mutations and gene expression patterns in cancer cells, they cannot detect tumour heterogeneity. However, single-cell technology has provided an ample opportunity to overcome this difficulty. Since this technology allows us to detect the heterogeneous properties of all cancer cells, this can further our knowledge of the signaling pathways in cancer cells. Indeed, single-cell transcriptomics technology has paved the road for identifying novel biomarkers and signaling pathways, which can serve as targets. This study aims to review the current knowledge about pathways involved in developing cancer cells and shed light on single-cell studies as promising therapeutic approaches.

scholarly journals Multimodal single-cell approaches shed light on T cell heterogeneity

2019 ◽  
Vol 61 ◽  
pp. 17-25 ◽  
Author(s):  
Aparna Nathan ◽  
Yuriy Baglaenko ◽  
Chamith Y Fonseka ◽  
Jessica I Beynor ◽  
Soumya Raychaudhuri
Keyword(s):  
T Cell ◽  
Single Cell ◽  
Cell Heterogeneity ◽  
Shed Light

scholarly journals Single-cell tracing of the first hematopoietic stem cell generation in human embryos

2019 ◽  
Author(s):  
Yang Zeng ◽  
Jian He ◽  
Zhijie Bai ◽  
Zongcheng Li ◽  
Yandong Gong ◽  
...  
Keyword(s):  
Stem Cells ◽  
Single Cell ◽  
Human Embryos ◽  
Cellular Interactions ◽  
Hematopoietic Stem ◽  
Human Embryogenesis ◽  
Genome Scale ◽  
Cellular Components ◽  
Shed Light ◽  
Carnegie Stage

AbstractTracing the emergence of the first hematopoietic stem cells (HSCs) in human embryos, particularly the scarce and transient precursors thereof, is so far challenging, largely due to technical limitations and material rarity. Here, using single-cell RNA sequencing, we constructed the first genome-scale gene expression landscape covering the entire course of endothelial-to-HSC transition during human embryogenesis. The transcriptomically defined HSC-primed hemogenic endothelial cells (ECs) were captured at Carnegie stage 12-14 in an unbiased way, showing an unambiguous arterial EC feature with the up-regulation ofRUNX1,MYBandANGPT1. Importantly, subcategorizing CD34+CD45−ECs into CD44+population strikingly enriched hemogenic ECs by over 10-fold. We further mapped the developmental path from arterial ECs via HSC-primed hemogenic ECs to hematopoietic stem progenitor cells, and revealed a distinct expression pattern of genes that were transiently over-represented upon the hemogenic fate choice of arterial ECs, includingEMCN,PROCRandRUNX1T1. We also uncovered another temporally and molecularly distinct intra-embryonic hemogenic EC population, which was detected mainly at earlier CS 10 and lacked the arterial feature. Finally, we revealed the cellular components of the putative aortic niche and potential cellular interactions acting on the HSC-primed hemogenic ECs. The cellular and molecular programs and interactions that underlie the generation of the first HSCs from hemogenic ECs in human embryos, together with distinguishing HSC-primed hemogenic ECs from others, will shed light on the strategies for the production of clinically useful HSCs from pluripotent stem cells.

scholarly journals P02.05 Comprehensive profiling of tumor heterogeneity and its microenvironment in advanced non-small cell lung cancer at single cell resolution

2021 ◽  
Vol 9 (Suppl 1) ◽  
pp. A9.2-A9
Author(s):  
Y Cordts ◽  
F Wu ◽  
J Fan ◽  
M Odenthal ◽  
R Buettner ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Microenvironment ◽  
Single Cell ◽  
Tumor Heterogeneity ◽  
Cell Types ◽  
Small Cell ◽  
Small Cell Lung ◽  
Part Time ◽  
Nsclc Patients ◽  
Shed Light

BackgroundLung cancer is a highly heterogeneous disease. Cancer cells and cells within the tumor microenvironment together determine disease progression, as well as response to or escape from treatment.Materials and MethodsTo map the cell type-specific transcriptome landscape of cancer cells and their tumor microenvironment in advanced non-small cell lung cancer (NSCLC), we analyzed 42 tissue biopsy samples from stage III/IV NSCLC patients by single cell RNA sequencing and presented the large scale, single cell resolution profiles of advanced NSCLCs.ResultsIn addition to cell types described in previous single cell studies of early stage lung cancer, we were able to identify new cell types such as follicular dendritic cells and T helper 17 cells. Tumors from different patients display large heterogeneity in cellular composition, chromosomal structure, developmental trajectory, intercellular signaling network and phenotype dominance. Our study also revealed a correlation of tumor heterogeneity with tumor associated neutrophils, which might help to shed light on their function in NSCLC.ConclusionsThis study presented first-time the tumor heterogeneity and tumor microenvironment profile from late-stage, largely untreated NSCLC patients, and shed light on possible treatment regimes.Disclosure InformationY. Cordts: A. Employment (full or part-time); Modest; Singleron Biotechnologies GmbH. F. Wu: None. J. Fan: A. Employment (full or part-time); Modest; Singleron Biotechnologies GmbH. M. Odenthal: None. R. Buettner: None. C. Zhou: None.

scholarly journals Single cell RNAseq uncovers a robust transcriptional response to morphine by oligodendrocytes

2018 ◽  
Author(s):  
Denis Avey ◽  
Sumithra Sankararaman ◽  
Aldrin K. Y. Yim ◽  
Ruteja Barve ◽  
Robi D. Mitra ◽  
...  
Keyword(s):  
Single Cell ◽  
Differential Expression Analysis ◽  
Transcriptional Response ◽  
Cell Types ◽  
Unfolded Protein ◽  
Cell Type Specific ◽  
Cellular Pathways ◽  
The Unfolded Protein Response ◽  
Protein Response ◽  
Shed Light

SUMMARYMolecular and behavioral responses to opioids are thought to be primarily mediated by neurons, although there is accumulating evidence that other cell types also play a role in drug addiction. To investigate cell-type-specific opioid responses, we performed single-cell RNA sequencing of the nucleus accumbens of mice following acute morphine treatment. Differential expression analysis uncovered robust morphine-dependent changes in gene expression in oligodendrocytes. We examined the expression of selected genes, including Cdkn1a and Sgk1, by FISH, confirming their induction by morphine in oligodendrocytes. Further analysis using RNAseq of FACS-purified oligodendrocytes revealed a large cohort of morphine-regulated genes. Importantly, the affected genes are enriched for roles in cellular pathways intimately linked to oligodendrocyte maturation and myelination, including the unfolded protein response. Altogether, our data shed light on a novel, morphine-dependent transcriptional response by oligodendrocytes that may contribute to the myelination defects observed in human opioid addicts.

scholarly journals Intracellular injection of phospholipids directly alters exocytosis and the fraction of chemical release in chromaffin cells as measured by nano-electrochemistry

2020 ◽  
Vol 11 (43) ◽  
pp. 11869-11876
Author(s):  
Mohaddeseh Aref ◽  
Elias Ranjbari ◽  
Armaghan Romiani ◽  
Andrew G. Ewing
Keyword(s):  
Chromaffin Cells ◽  
Secretory Cells ◽  
Intracellular Injection ◽  
Chemical Release ◽  
Intracellular Vesicle ◽  
Electrochemical Cytometry

Amperometry and intracellular vesicle impact electrochemical cytometry with nanotip electrodes were used to monitor the effects on exocytosis and vesicular storage after nano-injection of phospholipids with different geometries into secretory cells.

scholarly journals Challenges and Opportunities for the Translation of Single-Cell RNA Sequencing Technologies to Dermatology

Life ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 67
Author(s):  
Alex M. Ascensión ◽  
Marcos J. Araúzo-Bravo ◽  
Ander Izeta
Keyword(s):  
Single Cell ◽  
Single Cell Analysis ◽  
Cell Types ◽  
Cellular Level ◽  
Special Focus ◽  
Sequencing Technologies ◽  
Skin Cell ◽  
Challenges And Opportunities ◽  
Skin Biology ◽  
Shed Light

Skin is a complex and heterogeneous organ at the cellular level. This complexity is beginning to be understood through the application of single-cell genomics and computational tools. A large number of datasets that shed light on how the different human skin cell types interact in homeostasis—and what ceases to work in diverse dermatological diseases—have been generated and are publicly available. However, translation of these novel aspects to the clinic is lacking. This review aims to summarize the state-of-the-art of skin biology using single-cell technologies, with a special focus on skin pathologies and the translation of mechanistic findings to the clinic. The main implications of this review are to summarize the benefits and limitations of single-cell analysis and thus help translate the emerging insights from these novel techniques to the bedside.

scholarly journals Pseudo-mutant p53 as a targetable phenotype of DNMT3A-mutated pre-leukemia

2021 ◽  
Author(s):  
Amos Tuval ◽  
Yardena Brilon ◽  
Hadas Ezogy ◽  
Yoni Moskovitz ◽  
Tamir Biezuner ◽  
...  
Keyword(s):  
Single Cell ◽  
Dynamic Equilibrium ◽  
Selective Advantage ◽  
Mutant P53 ◽  
Wild Type ◽  
Similar Extent ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Gene Tp53 ◽  
Shed Light

Pre-leukemic clones carrying DNMT3A mutations have a selective advantage and an inherent chemo-resistance, however the basis for this phenotype has not been fully elucidated. Mutations affecting the gene TP53 occur in pre-leukemic hematopoietic stem/progenitor cells (preL-HSPCs) and lead to chemo-resistance. Many of these mutations cause a conformational change and some of them were shown to enhance self-renewal capacity of preL-HSPCs. Intriguingly, a misfolded p53 was described in AML blasts that do not harbor mutations in TP53, emphasizing the dynamic equilibrium between a wild-type (WT) and a pseudo-mutant conformations of p53. By combining single cell analyses and p53 conformation-specific monoclonal antibodies we studied preL-HSPCs from primary human DNMT3A AML samples. We found that while leukemic blasts express mainly the WT conformation, in preL-HSPCs the pseudo-mutant conformation is the dominant. HSPCs from non-leukemic samples expressed both conformations to a similar extent. Treatment with a short peptide that can shift the dynamic equilibrium favoring the WT conformation of p53, specifically eliminated preL-HSPCs that had dysfunctional canonical p53 pathway activity as reflected by single cell RNA sequencing. Our observations shed light upon a possible targetable p53 dysfunction in human preL-HSPCs carrying DNMT3A mutations. This opens new avenues for leukemia prevention.

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