Identification of Macrophage Genotype and Key Biological Pathways in Circulating Angiogenic Cell Transcriptome

Background. Circulating angiogenic cells (CAC) have been identified as important regulators of vascular biology. However, there is still considerable debate about the genotype and function of CAC. Methods and Results. Data from publicly available gene expression data sets were used to analyse the transcriptome of in vitro cultured CAC (CACiv). Genes and pathways of interest were further evaluated using qPCR comparing CACiv versus CD14+ monocytic cells. The CACiv transcriptome strongly related to tissue macrophages, and more specifically to regulatory M2c macrophages. The cytokine expression profile of CACiv was predominantly immune modulatory and resembled the cytokine expression of tumor-associated macrophages (TAM). Pathway analysis revealed previously unrecognized biological processes in CACiv, such as riboflavin metabolism and liver X receptor (LXR)/retinoid X receptor (RXR) and farnesoid X receptor (FXR)/retinoid X receptor (RXR) pathways. Analysis of endothelial-specific genes did not show evidence for endothelial transdifferentiation. Conclusions. CACiv are genotypically similar to regulatory M2c macrophages and lack signs of endothelial differentiation.

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Cytokine expression profile of in vitro cultured endometrial stromal and epithelial cells during the window of implantation (WOI) – a promising tool for receptivity assessment

10.26226/morressier.573c1512d462b80296c9864d ◽

2016 ◽

Author(s):

Todor Chaushev

Keyword(s):

Epithelial Cells ◽

Expression Profile ◽

Cytokine Expression ◽

Cytokine Expression Profile ◽

Promising Tool

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Mucosal-Associated Invariant T (MAIT) Cells Are Highly Activated and Functionally Impaired in COVID-19 Patients

Viruses ◽

10.3390/v13020241 ◽

2021 ◽

Vol 13 (2) ◽

pp. 241

Author(s):

Sebastian Deschler ◽

Juliane Kager ◽

Johanna Erber ◽

Lisa Fricke ◽

Plamena Koyumdzhieva ◽

...

Keyword(s):

T Cells ◽

Ex Vivo ◽

Severe Disease ◽

Mait Cells ◽

Cytokine Expression Profile ◽

Saps Ii Score ◽

Functionally Impaired ◽

Antiviral Function ◽

And Function

Coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), comprises mild courses of disease as well as progression to severe disease, characterised by lung and other organ failure. The immune system is considered to play a crucial role for the pathogenesis of COVID-19, although especially the contribution of innate-like T cells remains poorly understood. Here, we analysed the phenotype and function of mucosal-associated invariant T (MAIT) cells, innate-like T cells with potent antimicrobial effector function, in patients with mild and severe COVID-19 by multicolour flow cytometry. Our data indicate that MAIT cells are highly activated in patients with COVID-19, irrespective of the course of disease, and express high levels of proinflammatory cytokines such as IL-17A and TNFα ex vivo. Of note, expression of the activation marker HLA-DR positively correlated with SAPS II score, a measure of disease severity. Upon MAIT cell-specific in vitro stimulation, MAIT cells however failed to upregulate expression of the cytokines IL-17A and TNFα, as well as cytolytic proteins, that is, granzyme B and perforin. Thus, our data point towards an altered cytokine expression profile alongside an impaired antibacterial and antiviral function of MAIT cells in COVID-19 and thereby contribute to the understanding of COVID-19 immunopathogenesis.

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Transcriptomic characterization of signaling pathways associated with osteoblastic differentiation of MC-3T3E1 cells

10.1101/410597 ◽

2018 ◽

Author(s):

Louis M. Luttrell ◽

Moahad S. Dar ◽

Diane Gesty-Palmer ◽

Hesham M. El-Shewy ◽

Katherine M. Robinson ◽

...

Keyword(s):

Gene Expression ◽

Osteoblast Differentiation ◽

Mechanical Load ◽

Osteoblastic Differentiation ◽

Signaling Networks ◽

Mineral Density ◽

Pathways Analysis ◽

And Function ◽

Osteoblast Maturation

AbstractBone remodeling involves the coordinated actions of osteoclasts, which resorb the calcified bony matrix, and osteoblasts, which refill erosion pits created by osteoclasts to restore skeletal integrity and adapt to changes in mechanical load. Osteoblasts are derived from pluripotent mesenchymal stem cell precursors, which undergo differentiation under the influence of a host of local and environmental cues. To characterize the autocrine/paracrine signaling networks associated with osteoblast maturation and function, we performed gene network analysis using complementary “agnostic” DNA microarray and “targeted” NanoString™ nCounter datasets derived from murine MC3T3-E1 cells induced to undergo synchronized osteoblastic differentiation in vitro. Pairwise datasets representing changes in gene expression associated with growth arrest (day 2 to 5 in culture), differentiation (day 5 to 10 in culture), and osteoblast maturation (day 10 to 28 in culture) were analyzed using Ingenuity Systems™ Pathways Analysis to generate predictions about signaling pathway activity based on the temporal sequence of changes in target gene expression. Our data indicate that some pathways known to be involved in osteoblast differentiation, e.g. Wnt/β-catenin signaling, are most active early in the process, while others, e.g. TGFβ/BMP, cytokine/JAK-STAT and TNFα/RANKL signaling, increase in activity as differentiation progresses. Collectively, these pathways contribute to the sequential expression of genes involved in the synthesis and mineralization of extracellular matrix. These results provide insight into the temporal coordination and complex interplay between signaling networks controlling gene expression during osteoblast differentiation. A more complete understanding of these processes may aid the discovery of novel methods to promote osteoblast development for the trea™ent of conditions characterized by low bone mineral density.

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Molecular architecture and functions of the neuronal cytoskeleton

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100157541 ◽

1990 ◽

Vol 48 (3) ◽

pp. 2-3

Author(s):

Nobutaka Hirokawa

Keyword(s):

Major Elements ◽

Molecular Structures ◽

Organelle Transport ◽

Molecular Architecture ◽

Neuronal Morphogenesis ◽

Microtubule Associated Proteins ◽

Associated Proteins ◽

And Function ◽

Small Clusters

In this symposium I will present our studies about the molecular architecture and function of the cytomatrix of the nerve cells. The nerve cell is a highly polarized cell composed of highly branched dendrites, cell body, and a single long axon along the direction of the impulse propagation. Each part of the neuron takes characteristic shapes for which the cytoskeleton provides the framework. The neuronal cytoskeletons play important roles on neuronal morphogenesis, organelle transport and the synaptic transmission. In the axon neurofilaments (NF) form dense arrays, while microtubules (MT) are arranged as small clusters among the NFs. On the other hand, MTs are distributed uniformly, whereas NFs tend to run solitarily or form small fascicles in the dendrites Quick freeze deep etch electron microscopy revealed various kinds of strands among MTs, NFs and membranous organelles (MO). These structures form major elements of the cytomatrix in the neuron. To investigate molecular nature and function of these filaments first we studied molecular structures of microtubule associated proteins (MAP1A, MAP1B, MAP2, MAP2C and tau), and microtubules reconstituted from MAPs and tubulin in vitro. These MAPs were all fibrous molecules with different length and formed arm like projections from the microtubule surface.

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Decision letter for "Human monocytic myeloid‐derived suppressor cells impair B‐cell phenotype and function in vitro"

10.1002/eji.201948240/v2/decision1 ◽

2019 ◽

Keyword(s):

B Cell ◽

Suppressor Cells ◽

Cell Phenotype ◽

Myeloid Derived Suppressor Cells ◽

And Function

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Review for "Human monocytic myeloid‐derived suppressor cells impair B‐cell phenotype and function in vitro"

10.1002/eji.201948240/v1/review1 ◽

2019 ◽

Keyword(s):

B Cell ◽

Suppressor Cells ◽

Cell Phenotype ◽

Myeloid Derived Suppressor Cells ◽

And Function

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Role of the 807 C/T Polymorphism of the α2 Gene in Platelet GP Ia Collagen Receptor Expression and Function

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614605 ◽

1999 ◽

Vol 81 (06) ◽

pp. 951-956 ◽

Cited By ~ 59

Author(s):

J. Corral ◽

R. González-Conejero ◽

J. Rivera ◽

F. Ortuño ◽

P. Aparicio ◽

...

Keyword(s):

Venous Thrombosis ◽

Cell Types ◽

Receptor Expression ◽

Case Control Studies ◽

Platelet Surface ◽

Vitro Analysis ◽

And Function ◽

In Vitro Analysis

SummaryThe variability of the platelet GP Ia/IIa density has been associated with the 807 C/T polymorphism (Phe 224) of the GP Ia gene in American Caucasian population. We have investigated the genotype and allelic frequencies of this polymorphism in Spanish Caucasians. The T allele was found in 35% of the 284 blood donors analyzed. We confirmed in 159 healthy subjects a significant association between the 807 C/T polymorphism and the platelet GP Ia density. The T allele correlated with high number of GP Ia molecules on platelet surface. In addition, we observed a similar association of this polymorphism with the expression of this protein in other blood cell types. The platelet responsiveness to collagen was determined by “in vitro” analysis of the platelet activation and aggregation response. We found no significant differences in these functional platelet parameters according to the 807 C/T genotype. Finally, results from 3 case/control studies involving 302 consecutive patients (101 with coronary heart disease, 104 with cerebrovascular disease and 97 with deep venous thrombosis) determined that the 807 C/T polymorphism of the GP Ia gene does not represent a risk factor for arterial or venous thrombosis.

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