scholarly journals Cooperative cell invasion: matrix metalloproteinase–mediated incorporation between cells

2016 ◽  
Vol 27 (21) ◽  
pp. 3284-3292 ◽  
Author(s):  
Camilla B. Mitchell ◽  
Geraldine M. O’Neill
Keyword(s):  
Matrix Metalloproteinase ◽  
Single Cells ◽  
Neuroblastoma Cells ◽  
Complex Mixture ◽  
Cell Types ◽  
Cell Populations ◽  
Bone Lesions ◽  
Collagen Gels ◽  
Multicellular Spheroids

Progression to metastatic disease is a leading cause of cancer death. Tumors are a complex mixture of cell types, both genetically heterogeneous malignant cells and associated nonmalignant cells. Models mimicking this heterogeneous cell environment have revealed that invasive cell populations can induce dissemination by otherwise poorly/noninvasive tumor cells, known as cooperative invasion. Neuroblastoma tumors arise in children and are characterized by mixed cellular populations in vivo, consisting chiefly of neuronal (N)-type and substrate (S)-type cells. The S-type cells have all the hallmarks of invasive leader cell populations and have been coisolated with N-type cells from metastatic bone lesions, but to date their ability to induce cooperative invasion has not been investigated. Therefore, in the present study, we analyzed the invasive behavior of mixed N-type and S-type multicellular spheroids embedded in three-dimensional collagen gels. Our analyses show that S-type cells induce invasion of either single cells or small cell clusters of N-type cells. In contrast to other reports of cooperative invasion in which mixed cultures exhibit a follow-the-leader mechanism, we show coincident emergence of S- and N-type cells from mixed spheroids. Our data suggest mutual effects between the two cell types. Thus, whereas coculture with S-type cells induces N-type invasion, coculture with N-type cells slows S-type invasion. Using matrix metalloproteinase (MMP) inhibitors and cell incorporation assays, we demonstrate that MMP activity is required for S-type cells to insert into layers of N-type cells. Our study therefore highlights an important role for S-type neuroblastoma cells in the invasion process and reveals a new mechanism of cooperative invasion.

scholarly journals Chemogenetic Tools for Causal Cellular and Neuronal Biology

2018 ◽  
Vol 98 (1) ◽  
pp. 391-418 ◽  
Author(s):  
Deniz Atasoy ◽  
Scott M. Sternson
Keyword(s):  
G Protein ◽  
Ex Vivo ◽  
Cell Types ◽  
Cell Populations ◽  
Specific Cell ◽  
Cellular Processes ◽  
Distinct Cell ◽  
G Protein Coupled ◽  
Pharmacological Control

Chemogenetic technologies enable selective pharmacological control of specific cell populations. An increasing number of approaches have been developed that modulate different signaling pathways. Selective pharmacological control over G protein-coupled receptor signaling, ion channel conductances, protein association, protein stability, and small molecule targeting allows modulation of cellular processes in distinct cell types. Here, we review these chemogenetic technologies and instances of their applications in complex tissues in vivo and ex vivo.

scholarly journals Evidence for heterophilic adhesion of embryonic retinal cells and neuroblastoma cells to substratum-adsorbed NCAM

1992 ◽  
Vol 117 (6) ◽  
pp. 1311-1320 ◽  
Author(s):  
BA Murray ◽  
JJ Jensen
Keyword(s):  
Neuroblastoma Cells ◽  
Cell Types ◽  
Antibody Fragments ◽  
Adhesion Assay ◽  
Temperature Dependent ◽  
Retinal Cells ◽  
Embryonic Chicken ◽  
Surface Ligand ◽  
Solid Substratum

The adhesion of embryonic chicken retinal cells and mouse N2A neuroblastoma cells to purified embryonic chicken retinal NCAM adsorbed on a solid substratum was examined using a quantitative centrifugal adhesion assay. Both cell types adhered to NCAM and the adhesion was specifically inhibited by monovalent anti-NCAM antibody fragments. N2A cell adhesion depended on the amount of NCAM applied to the substratum, was cation independent, and was insensitive to treatment with the cytoskeletal perturbing drugs colchicine and cytochalasin D. These results indicated that the tubulin and actin cytoskeletons were not critically required for adhesion to NCAM and make it unlikely that the cell surface ligand for NCAM is an integrin. Adhesion was however temperature dependent, strengthening greatly after a brief incubation at 37 degrees C. CHO cells transfected with NCAM cDNAs did not adhere specifically to substratum-bound NCAM and pretreatment of N2A cells and retinal cells with anti-NCAM antibodies did not inhibit adhesion to substratum-bound NCAM. These results suggest that a heterophilic interaction between substratum-adsorbed NCAM and a non-NCAM ligand on the surface of the probe cells affects adhesion in this system and support the possibility that heterophilic adhesion may be a function of NCAM in vivo.

scholarly journals Homogentisic acid-derived pigment as a biocompatible label for optoacoustic imaging of macrophages

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Ina Weidenfeld ◽  
Christian Zakian ◽  
Peter Duewell ◽  
Andriy Chmyrov ◽  
Uwe Klemm ◽  
...  
Keyword(s):  
Single Cells ◽  
Cell Types ◽  
Homogentisic Acid ◽  
Tissue Imaging ◽  
Whole Body ◽  
Whole Body Imaging ◽  
Optoacoustic Imaging ◽  
Pigment Formation ◽  
Functionally Diverse

Abstract Macrophages are one of the most functionally-diverse cell types with roles in innate immunity, homeostasis and disease making them attractive targets for diagnostics and therapy. Photo- or optoacoustics could provide non-invasive, deep tissue imaging with high resolution and allow to visualize the spatiotemporal distribution of macrophages in vivo. However, present macrophage labels focus on synthetic nanomaterials, frequently limiting their ability to combine both host cell viability and functionality with strong signal generation. Here, we present a homogentisic acid-derived pigment (HDP) for biocompatible intracellular labeling of macrophages with strong optoacoustic contrast efficient enough to resolve single cells against a strong blood background. We study pigment formation during macrophage differentiation and activation, and utilize this labeling method to track migration of pro-inflammatory macrophages in vivo with whole-body imaging. We expand the sparse palette of macrophage labels for in vivo optoacoustic imaging and facilitate research on macrophage functionality and behavior.

scholarly journals A human cell atlas of fetal chromatin accessibility

Science ◽  
2020 ◽  
Vol 370 (6518) ◽  
pp. eaba7612 ◽  
Author(s):  
Silvia Domcke ◽  
Andrew J. Hill ◽  
Riza M. Daza ◽  
Junyue Cao ◽  
Diana R. O’Day ◽  
...  
Keyword(s):  
Gene Expression ◽  
Human Cell ◽  
Single Cells ◽  
Complex Trait ◽  
Cell Types ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
Cell Type ◽  
Cell Type Specific

The chromatin landscape underlying the specification of human cell types is of fundamental interest. We generated human cell atlases of chromatin accessibility and gene expression in fetal tissues. For chromatin accessibility, we devised a three-level combinatorial indexing assay and applied it to 53 samples representing 15 organs, profiling ~800,000 single cells. We leveraged cell types defined by gene expression to annotate these data and cataloged hundreds of thousands of candidate regulatory elements that exhibit cell type–specific chromatin accessibility. We investigated the properties of lineage-specific transcription factors (such as POU2F1 in neurons), organ-specific specializations of broadly distributed cell types (such as blood and endothelial), and cell type–specific enrichments of complex trait heritability. These data represent a rich resource for the exploration of in vivo human gene regulation in diverse tissues and cell types.

In vitro evaluation of cobalt oxide nanoparticle-induced toxicity

2017 ◽  
Vol 33 (8) ◽  
pp. 646-654 ◽  
Author(s):  
Mahmoud Abudayyak ◽  
Tuba Altincekic Gurkaynak ◽  
Gül Özhan
Keyword(s):  
Nervous System ◽  
Cobalt Oxide ◽  
Cell Lines ◽  
Neuroblastoma Cells ◽  
A549 Cells ◽  
Cell Types ◽  
Carcinoma Cells ◽  
High Exposure

Cobalt oxide (Co3O4) nanoparticles have applications in nanomedicine and nanotechnology; therefore, any possible adverse effects require thorough investigation. The present study investigated the effects of Co3O4 nanoparticles on four different cell lines: liver, HepG2 hepatocellular carcinoma cells; lung, A549 lung carcinoma cells; gastrointestinal, Caco-2 colorectal adenocarcinoma cells; and nervous system, SH-SY5Y neuroblastoma cells. A difference was observed in cell sensitivity toward Co3O4 nanoparticles. Co3O4 nanoparticles were taken up by all the cell types. However, no cell death was observed in HepG2, Caco-2, or SH-SY5Y cells; only A549 cells showed cytotoxicity at relatively high exposure concentrations. Co3O4 nanoparticles did not induce DNA damage or apoptosis in the cell lines tested except in A549. Interestingly, Co3O4 nanoparticles induced cellular oxidative damage in all cell types except Caco-2, resulting in increased malondialdehyde and 8-hydroxydeoxyguanosine levels and decreased glutathione levels. According to our results, it could be indicated that high concentrations of Co3O4 nanoparticles affected the pulmonary system but were unlikely to affect the liver, nervous system, or gastrointestinal system. Co3O4 nanoparticles might be safely used for industrial, commercial, and nanomedical applications if dose rates are adjusted depending on the route of exposure. However, further in vivo and in vitro studies are required to confirm the safety of Co3O4 nanoparticles.

scholarly journals Steviol Glycosides Modulate Glucose Transport in Different Cell Types

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Benedetta Rizzo ◽  
Laura Zambonin ◽  
Cristina Angeloni ◽  
Emanuela Leoncini ◽  
Francesco Vieceli Dalla Sega ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Glucose Transport ◽  
Molecular Mechanisms ◽  
Neuroblastoma Cells ◽  
Stevia Rebaudiana ◽  
Cell Types ◽  
Akt Pathway ◽  
Steviol Glycosides ◽  
Human Neuroblastoma

Extracts fromStevia rebaudianaBertoni, a plant native to Central and South America, have been used as a sweetener since ancient times. Currently,Steviaextracts are largely used as a noncaloric high-potency biosweetener alternative to sugar, due to the growing incidence of type 2 diabetes mellitus, obesity, and metabolic disorders worldwide. Despite the large number of studies onSteviaand steviol glycosidesin vivo, little is reported concerning the cellular and molecular mechanisms underpinning the beneficial effects on human health. The effect of four commercialSteviaextracts on glucose transport activity was evaluated in HL-60 human leukaemia and in SH-SY5Y human neuroblastoma cells. The extracts were able to enhance glucose uptake in both cellular lines, as efficiently as insulin. Our data suggest that steviol glycosides could act by modulating GLUT translocation through the PI3K/Akt pathway since treatments with both insulin andSteviaextracts increased the phosphorylation of PI3K and Akt. Furthermore,Steviaextracts were able to revert the effect of the reduction of glucose uptake caused by methylglyoxal, an inhibitor of the insulin receptor/PI3K/Akt pathway. These results corroborate the hypothesis thatSteviaextracts could mimic insulin effects modulating PI3K/Akt pathway.

scholarly journals CD8 single-cell gene coexpression reveals three different effector types present at distinct phases of the immune response

2007 ◽  
Vol 204 (5) ◽  
pp. 1193-1205 ◽  
Author(s):  
António Peixoto ◽  
César Evaristo ◽  
Ivana Munitic ◽  
Marta Monteiro ◽  
Alain Charbit ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Cd8 T Cells ◽  
Cytotoxic T Cells ◽  
Single Cells ◽  
Cell Types ◽  
Primary Response ◽  
Gene Coexpression

To study in vivo CD8 T cell differentiation, we quantified the coexpression of multiple genes in single cells throughout immune responses. After in vitro activation, CD8 T cells rapidly express effector molecules and cease their expression when the antigen is removed. Gene behavior after in vivo activation, in contrast, was quite heterogeneous. Different mRNAs were induced at very different time points of the response, were transcribed during different time periods, and could decline or persist independently of the antigen load. Consequently, distinct gene coexpression patterns/different cell types were generated at the various phases of the immune responses. During primary stimulation, inflammatory molecules were induced and down-regulated shortly after activation, generating early cells that only mediated inflammation. Cytotoxic T cells were generated at the peak of the primary response, when individual cells simultaneously expressed multiple killer molecules, whereas memory cells lost killer capacity because they no longer coexpressed killer genes. Surprisingly, during secondary responses gene transcription became permanent. Secondary cells recovered after antigen elimination were more efficient killers than cytotoxic T cells present at the peak of the primary response. Thus, primary responses produced two transient effector types. However, after boosting, CD8 T cells differentiate into long-lived killer cells that persist in vivo in the absence of antigen.

scholarly journals A Model for Spheroid versus Monolayer Response of SK-N-SH Neuroblastoma Cells to Treatment with 15-Deoxy-PGJ2

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Dorothy I. Wallace ◽  
Ann Dunham ◽  
Paula X. Chen ◽  
Michelle Chen ◽  
Milan Huynh ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Neuroblastoma Cells ◽  
Response To Treatment ◽  
Data Sets ◽  
Tumor Spheroid ◽  
Multicellular Spheroids ◽  
Treatment Data ◽  
The Difference

Researchers have observed that response of tumor cells to treatment varies depending on whether the cells are grown in monolayer, asin vitrospheroids orin vivo. This study uses data from the literature on monolayer treatment of SK-N-SH neuroblastoma cells with 15-deoxy-PGJ2and couples it with data on growth rates for untreated SK-N-SH neuroblastoma cells grown as multicellular spheroids. A linear model is constructed for untreated and treated monolayer data sets, which is tuned to growth, death, and cell cycle data for the monolayer case for both control and treatment with 15-deoxy-PGJ2. The monolayer model is extended to a five-dimensional nonlinear model ofin vitrotumor spheroid growth and treatment that includes compartments of the cell cycle (G1,S,G2/M) as well as quiescent (Q) and necrotic (N) cells. Monolayer treatment data for 15-deoxy-PGJ2is used to derive a prediction of spheroid response under similar treatments. For short periods of treatment, spheroid response is less pronounced than monolayer response. The simulations suggest that the difference in response to treatment of monolayer versus spheroid cultures observed in laboratory studies is a natural consequence of tumor spheroid physiology rather than any special resistance to treatment.

scholarly journals High-Dimensional Single-Cell Quantitative Profiling of Skeletal Muscle Cell Population Dynamics during Regeneration

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1723
Author(s):  
Lucia Lisa Petrilli ◽  
Filomena Spada ◽  
Alessandro Palma ◽  
Alessio Reggio ◽  
Marco Rosina ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Single Cells ◽  
Cell Types ◽  
Interstitial Space ◽  
Cell Populations ◽  
Wild Type ◽  
Mass Cytometry ◽  
Pathological Conditions ◽  
Comprehensive Picture ◽  
Quantitative Profiling

The interstitial space surrounding the skeletal muscle fibers is populated by a variety of mononuclear cell types. Upon acute or chronic insult, these cell populations become activated and initiate finely-orchestrated crosstalk that promotes myofiber repair and regeneration. Mass cytometry is a powerful and highly multiplexed technique for profiling single-cells. Herein, it was used to dissect the dynamics of cell populations in the skeletal muscle in physiological and pathological conditions. Here, we characterized an antibody panel that could be used to identify most of the cell populations in the muscle interstitial space. By exploiting the mass cytometry resolution, we provided a comprehensive picture of the dynamics of the major cell populations that sensed and responded to acute damage in wild type mice and in a mouse model of Duchenne muscular dystrophy. In addition, we revealed the intrinsic heterogeneity of many of these cell populations.

scholarly journals A human cell atlas of fetal gene expression

Science ◽  
2020 ◽  
Vol 370 (6518) ◽  
pp. eaba7721 ◽  
Author(s):  
Junyue Cao ◽  
Diana R. O’Day ◽  
Hannah A. Pliner ◽  
Paul D. Kingsley ◽  
Mei Deng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Human Cell ◽  
Human Gene ◽  
Single Cells ◽  
Cell Types ◽  
Chromatin Accessibility ◽  
Fundamental Interest ◽  
Organ Specific ◽  
Expression Program

The gene expression program underlying the specification of human cell types is of fundamental interest. We generated human cell atlases of gene expression and chromatin accessibility in fetal tissues. For gene expression, we applied three-level combinatorial indexing to >110 samples representing 15 organs, ultimately profiling ~4 million single cells. We leveraged the literature and other atlases to identify and annotate hundreds of cell types and subtypes, both within and across tissues. Our analyses focused on organ-specific specializations of broadly distributed cell types (such as blood, endothelial, and epithelial), sites of fetal erythropoiesis (which notably included the adrenal gland), and integration with mouse developmental atlases (such as conserved specification of blood cells). These data represent a rich resource for the exploration of in vivo human gene expression in diverse tissues and cell types.

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