Cell Communication Mechanisms Research Articles

Obesity-derived macrophages upregulate TNF-α to induce apoptosis in glial cell via the NF-κB/PHLPP1 axis

Macrophages in obese adipose tissue have been shown to damage nerve fibers, however, the mechanism underlying how macrophages cause glial cell damage remains unknown. This study aimed to characterize the mechanism by which macrophages induce apoptosis in glial cell during obesity formation in mice by single-nucleus RNA sequencing (snRNA-seq). Cells obtained from paraepididymal adipose tissue in obese mice underwent snRNA-seq. Eighteen different clusters were identified, and 12 cell types were annotated, including glial cells, macrophages, and fibroblasts. There was a negative correlation between the number of glial cells and macrophages in mouse adipose tissue during the formation of obesity. The pro-apoptotic factor PHLPP1 was identified in GO Terms. The interaction between adipose tissue glial cells and macrophages was revealed via in-depth analysis, and the cell–cell communication mechanism between the TNF-α and NF-KB/PHLPP1 axes was perfected. Apoptosis of glial cell by upregulation of TNF-α via obesity-derived macrophages and activation of the NF-κB/PHLPP1 axis. We further revealed how macrophages induce apoptosis in glial cells during obesity formation, as well as different changes in the two cell populations. This study provides valuable resources and foundations for understanding the mechanistic effects of macrophages and glial cells during obesity formation, as well as diseases and potential interventions.

Medical Scope of Biofilm and Quorum Sensing during Biofilm Formation: Systematic Review

Biofilms are accumulations of microorganisms in an extracellular polymeric substance matrix which are composed of polysaccharides, proteins, lipids, and nucleic acids. Many bacteria can switch between a planktonic form and a biofilm form. The planktonic bacteria have relatively high cell growth and reproduction rates and have a reduced likelihood of survival but can adapt to occupy new habitats. The biofilm state appears to be a natural and predominant state of bacteria. The need for the formation of bacterial biofilm is that it enhances the tolerance of bacteria to harsh environmental conditions, thereby allowing bacteria to avoid being washed away by water flow or the bloodstream by simply attaching to a surface or tissue, and the EPS matrix protects bacteria cells, in deeper layers, against antimicrobial agents, probably by limiting the diffusion of these agents. Biofilm formation steps are initial contact/attachment to the surface, followed by micro-colony formation, maturation and formation of the architecture of the biofilm, and finally detachment/dispersion of the biofilm. Once formed, biofilm restricts bacterial mobility and increases cell density. Secretions of autoinducers into the environment are critical for cross-signaling between bacteria. This cross-talk is called quorum sensing (QS). Quorum sensing is a cell–cell communication mechanism between bacteria that allows specific processes to be controlled, such as biofilm formation and virulence factor expression. Bacterial quorum sensing signaling mainly consists of acyl-homoserine lactones (produced by Gram-negatives), autoinducing peptides (produced by Gram-positives), and autoinducer-2 (produced by both Gram-negatives and Gram-positives). Therefore, this review is aimed at how bacterial biofilms work and are formed.

Single-cell combined with transcriptome sequencing to explore the molecular mechanism of cell communication in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a common, chronic, and progressive lung disease that severely impacts human health and survival. However, the intricate molecular underpinnings of IPF remains elusive. This study aims to delve into the nuanced molecular interplay of cellular interactions in IPF, thereby laying the groundwork for innovative therapeutic approaches in the clinical field of IPF. Sophisticated bioinformatics methods were employed to identify crucial biomarkers essential for the progression of IPF. The GSE122960 single-cell dataset was obtained from the Gene Expression Omnibus (GEO) compendium, and intercellular communication potentialities were scrutinized via CellChat. The random survival forest paradigm was established using the GSE70866 dataset. Quintessential genes were selected through Kaplan-Meier (KM) curves, while immune infiltration examinations, functional enrichment critiques and nomogram paradigms were inaugurated. Analysis of intercellular communication revealed an intimate potential connections between macrophages and various cell types, pinpointing five cardinal genes influencing the trajectory and prognosis of IPF. The nomogram paradigm, sculpted from these seminal genes, exhibits superior predictive prowess. Our research meticulously identified five critical genes, confirming their intimate association with the prognosis, immune infiltration and transcriptional governance of IPF. Interestingly, we discerned these genes' engagement with the EPITHELIAL_MESENCHYMAL_TRANSITION signalling pathway, which may enhance our understanding of the molecular complexity of IPF.

ID4-dependent secretion of VEGFA enhances the invasion capability of breast cancer cells and activates YAP/TAZ via integrin β3-VEGFR2 interaction

Understanding the mechanisms of breast cancer cell communication underlying cell spreading and metastasis formation is fundamental for developing new therapies. ID4 is a proto-oncogene overexpressed in the basal-like subtype of triple-negative breast cancer (TNBC), where it promotes angiogenesis, cancer stem cells, and BRACA1 misfunction. Here, we show that ID4 expression in BC cells correlates with the activation of motility pathways and promotes the production of VEGFA, which stimulates the interaction of VEGFR2 and integrin β3 in a paracrine fashion. This interaction induces the downstream focal adhesion pathway favoring migration, invasion, and stress fiber formation. Furthermore, ID4/ VEGFA/ VEGFR2/ integrin β3 signaling stimulates the nuclear translocation and activation of the Hippo pathway member’s YAP and TAZ, two critical executors for cancer initiation and progression. Our study provides new insights into the oncogenic roles of ID4 in tumor cell migration and YAP/TAZ pathway activation, suggesting VEGFA/ VEGFR2/ integrin β3 axis as a potential target for BC treatment.

Inhibition of Quorum Sensing to Mitigate the Risks of Membrane Biofouling in Biological Wastewater Treatment

Membrane-based systems play a pivotal role in various applications, providing efficient separation, purification, and filtration processes across diverse industries such as water purification and desalination. However, this system faces major challenge of membrane biofouling impacting the efficiency and sustainability of such systems. Biofouling occurs when various microorganisms like bacteria, fungi, etc. adheres to the surface of membrane and form biofilm which results in reducing membrane permeability and increasing its operational cost. Various physical, chemical and biological strategies are known to prevent biofouling. Inhibition of quorum sensing is a recent trend based on the researches that shows quorum sensing as an integral part of biofilm formation. Bacteria’s uses cell to cell communication mechanisms known as Quorum sensing, plays an important role in formation of virulence factors, biofilm. It is regulated by quorum sensing signalling molecules known as autoinducers like Autoinducing peptides, acyl homoserine lactones, Autoinducer-2. Various strategies can be adopted to inhibit quorum sensing: inhibition of Autoinducer synthase which is responsible for synthesizing autoinducers; inhibition/degradation of autoinducers and interfering with signal receptors. This article provides deeper knowledge of Quorum sensing (QS), methods of QS inhibition: Quorum quenching which involves the enzymatic degradation of QS signaling molecules, and the use of Quorum sensing inhibitor compounds in preventing membrane biofouling are discussed in detail. This article delves into the potential of disrupting quorum sensing pathways to prevent or reduce biofilm formation, thereby enhancing the performance and longevity of membranes in wastewater treatment. The mitigation of biofouling can revolutionize membrane-based systems, ensuring their sustainability and efficacy in water treatment processes

New EV nucleus in northern Germany - The Hamburg EV community: A present reality with a promising future

On April 13-14th, 2023, more than 50 researchers located in Hamburg, mainly working at the University Medical Center Hamburg-Eppendorf (UKE), met to present research projects focusing on extracellular vesicles (EVs). The meeting was supported by State Research Funding (LFF-FV74: Mechanisms of cell communication in Infection; Speaker Maura Dandri, UKE), which aims to develop existing and promising research areas further. This meeting certainly surpassed all expectations: what was first organized as a tentative get-together between a dozen EV scientists, soon revealed the existence of a much broader and strong EV community with more than 50 basic researchers and clinicians currently active in Hamburg. This first UKE-EV meeting created a platform to share experiences, projects, and protocols and mainly discuss future requirements to create a consolidated structure and network in Hamburg, enabling state-of-the-art EV research.

The time-resolved genomic impact of Wnt/β-catenin signaling.

Wnt signaling orchestrates gene expression via its effector, β-catenin. However, it is unknown whether β-catenin binds its target genomic regions simultaneously and how this impacts chromatin dynamics to modulate cell behavior. Using a combination of time-resolved CUT&RUN against β-catenin, ATAC-seq, and perturbation assays in different cell types, we show that Wnt/β-catenin physical targets are tissue-specific, β-catenin "moves" on different loci over time, and its association to DNA accompanies changing chromatin accessibility landscapes that determine cell behavior. In particular, Wnt/β-catenin progressively shapes the chromatin of human embryonic stem cells (hESCs) as they undergo mesodermal differentiation, a behavior that we define as "plastic." In HEK293T cells, on the other hand, Wnt/β-catenin drives a transient chromatin opening, followed by re-establishment of the pre-stimulation state, a response that we define as "elastic." Future experiments shall assess whether other cell communication mechanisms, in addition to Wnt signaling, are ruled by time, cellular idiosyncrasies, and chromatin constraints. A record of this paper's transparent peer review process is included in the supplemental information.

A mechanobiological model for tumor spheroid evolution with application to glioblastoma: A continuum multiphysics approach

Background:Spheroids are in vitro quasi-spherical structures of cell aggregates, eventually cultured within a hydrogel matrix, that are used, among other applications, as a technological platform to investigate tumor formation and evolution. Several interesting features can be replicated using this methodology, such as cell communication mechanisms, the effect of gradients of nutrients, or the creation of realistic 3D biological structures. The main objective of this work is to link the spheroid evolution with the mechanical activity of cells, coupled with nutrient consumption and the subsequent cell dynamics. Method:We propose a continuum mechanobiological model which accounts for the most relevant phenomena that take place in tumor spheroid evolution under in vitro suspension, namely, nutrient diffusion in the spheroid, kinetics of cellular growth and death, and mechanical interactions among the cells. The model is qualitatively validated, after calibration of the model parameters, versus in vitro experiments of spheroids of different glioblastoma cell lines. Results:Our model is able to explain in a novel way quite different setups, such as spheroid growth (up to six times the initial configuration for U-87 MG cell line) or shrinking (almost half of the initial configuration for U-251 MG cell line); as the result of the mechanical interplay of cells driven by cellular evolution. Conclusions:Glioblastoma tumor spheroid evolution is driven by mechanical interactions of the cell aggregate and the dynamical evolution of the cell population. All this information can be used to further investigate mechanistic effects in the evolution of tumors and their role in cancer disease.

Abstract P3075: Hippo Pathway In Cardiac Fibroblast Regulates Macrophage Recruitment Following Injury

Background: The evolutionary conserved Hippo signaling pathway (HSP) is an inhibitor of tissue regeneration, including the Lats1/2 kinases that phosphorylate and inactivate YAP and TAZ. Emerging data indicate that HSP regulates innate immunity, inflammation, and autoimmune diseases. However, the role of HSP in post-MI inflammation is poorly understood. Methods: Single-cell RNA-sequencing (scRNA-Seq) and spatial transcriptomics were utilized in cardiac fibroblast (CF)-specific-Lats1/2 knockout (Lats CKO) mouse heart. Flow cytometry, immunofluorescence (IF), and echocardiogram (Echo) were used to describe the phenotype in ventricle of Lats CKO mouse heart with/out Ccr2 knockout. Results: We integrated our scRNA-Seq data in Lats CKO mouse heart with three published data sets of MI mouse heart. A CF subcluster with elevated YAP activity and expressing chemokines Ccl2 and Ccl7 (Ccl2/Ccl7+ CFs) and macrophages (Macs) expressing Ccr2, the receptor for Ccl2/Ccl7 (Ccr2+ Macs), were identified, which suggests a signaling transduction from Ccl2/Ccl7+ CFs to Ccr2+ Macs in post-MI hearts. To figure out the function and mechanism of this specific cell communication, we employed a Lats CKO mice model which mimics the post-MI heart and exhibits high YAP activity and conformed the cell communication between Ccl2/Ccl7+ CFs and Ccr2+ Macs by spatial transcriptomics. Furthermore, Ccr2 loss of function in Lats CKO mice suppressed Mac expansion and CF proliferation. Consistently, Ccr2 knockout reversed the phenotype presenting smaller left ventricle chamber in Lats CKO mouse heart because of CF proliferation. Conclusion: YAP target genes Ccl2 and Ccl7 in CFs are responsible for Ccr2+ Macs recruitment and the recruited Ccr2+ Macs in turn promote CF proliferation post-MI.

Label-Free Quantification of Molecular Interaction in Live Red Blood Cells by Tracking Nanometer Scale Membrane Fluctuations.

Molecular interactions in live cells play an important role in both cellular functions and drug discovery. Current methods for measuring binding kinetics involve extracting the membrane protein and labeling, while the in situ quantification of molecular interaction with surface plasmon resonance (SPR) imaging mainly worked with fixed cells due to the micro-motion related noises of live cells. Here, an optical imaging method is presented to measure the molecular interaction with live red blood cells by tracking the nanometer membrane fluctuations. The membrane fluctuation dynamics are measured by tracking the membrane displacement during glycoprotein interaction. The data are analyzed with a thermodynamic model to determine the elastic properties of the cell observing reduced membrane fluctuations under fixatives, indicating cell fixations affect membrane mechanical properties. The binding kinetics of glycoprotein to several lectins are obtainedby tracking the membrane fluctuation amplitude changes on single live cells. The binding kinetics and strength of different lectins are quite different, indicating the glycoproteins expression heterogeneity in single cells. It is anticipated that the method will contribute to the understanding of mechanisms of cell interaction and communication, and have potential applications in the mechanical assessment of cancer or other diseases at the single-cell level, and screening of membrane protein targeting drugs.

Exploring communication signals inside the microbial community of a Listeria monocytogenes-carrying biofilm contamination site

In nature, bacterial pathogens like L. monocytogenes, live in nature associated with other microbial species in spatially-structured communities called biofilms. In the food industry, biofilms contribute to the survival and persistence of L. monocytogenes within processing facilities, thereby enhancing its risk of cross-contaminating food products. The challenge of combating biofilms has triggered the search for new antibiofilm strategies including devising ways to interfere with cell communication mechanisms (quorum-sensing) that are known to be involved with biofilm development regulation. The aim of this study was to explore cell communication signals in a L. monocytogenes-carrying microbial community isolated from a meat processing plant (location No. 96) in order to elucidate the ecological interactions that could serve as a starting point for the development of new antibiofilm strategies. Quorum quenching (QQ) and quorum sensing (QS) activities were screened among 31 bacterial strains isolated from location No. 96. Whereas no QQ activity was detected against short-chain lactone N-hexanoyl-DL-homoserine lactone (C6-HSL), it was detected against N-dodecanoyl-DL-homoserine lactone (C12-HSL) in 7 isolates (23%), particularly in Pseudomonas monteilli, Rhodococcus sp. and Rhodococcus erythropolis. QS activity assays detected HC4, C4, C6, OC6, HC10 and C16 in all the extracts, being C4, C6 and OC6 with predominantly produced by Pseudomonas monteilli, Pseudomonas gesardii, Psychrobacter maritimus and Paracoccus sp. High production levels of C16-HSL by Paracoccus sp. and the role of this long-chain lactone as a self-inhibitor of cell aggregation led us to carry out further studies focused on the effects of a Paracoccus lactone extract (PLE) against the biofilm formation by L. monocytogenes. A quantitative microscopic analysis demonstrated a significant decrease (p < 0.05) in the area occupied by biofilms formed on stainless steel (SS) coupons by different strains of L. monocytogenes in the presence of PLEs. Conversely, no significant differences were observed in the total number of viable adhered cells on SS coupons with or without PLE. The observed effect was partially reproduced by the addition of pure C16-HSL to 24 h-biofilms of L. monocytogenes L1.96. These results demonstrate that the observed effects can be attributed, at least partially, to the HSLs contained in the PLE. Overall, the present results highlight how interspecies communication within a biofilm can open up new insights for the development of new ways to combat biofilm.

Human Cardiac Progenitor Cell-Derived Extracellular Vesicles Exhibit Promising Potential for Supporting Cardiac Repair in Vitro

Although human Cardiac Progenitor Cells (hCPCs) are not retained by host myocardium they still improve cardiac function when injected into ischemic heart. Emerging evidence supports the hypothesis that hCPC beneficial effects are induced by paracrine action on resident cells. Extracellular vesicles (EVs) are an intriguing mechanism of cell communication based on the transport and transfer of peptides, lipids, and nucleic acids that have the potential to modulate signaling pathways, cell growth, migration, and proliferation of recipient cells. We hypothesize that EVs are involved in the paracrine effects elicited by hCPCs and held accountable for the response of the infarcted myocardium to hCPC-based cell therapy. To test this theory, we collected EVs released by hCPCs isolated from healthy myocardium and evaluated the effects they elicited when administered to resident hCPC and cardiac fibroblasts (CFs) isolated from patients with post-ischemic end-stage heart failure. Evidence emerging from our study indicated that hCPC-derived EVs impacted upon proliferation and survival of hCPCs residing in the ischemic heart and regulated the synthesis and deposition of extracellular-matrix by CFs. These findings suggest that beneficial effects exerted by hCPC injection are, at least to some extent, ascribable to the delivery of signals conveyed by EVs.

Redesigning regulatory components of quorum-sensing system for diverse metabolic control

Quorum sensing (QS) is a ubiquitous cell–cell communication mechanism that can be employed to autonomously and dynamically control metabolic fluxes. However, since the functions of genetic components in the circuits are not fully understood, the developed QS circuits are still less sophisticated for regulating multiple sets of genes or operons in metabolic engineering applications. Here, we discover the regulatory roles of a CRP-binding site and the lux box to −10 region within luxR-luxI intergenic sequence in controlling the lux-type QS promoters. By varying the numbers of the CRP-binding site and redesigning the lux box to −10 site sequence, we create a library of QS variants that possess both high dynamic ranges and low leakiness. These circuits are successfully applied to achieve diverse metabolic control in salicylic acid and 4-hydroxycoumarin biosynthetic pathways in Escherichia coli. This work expands the toolbox for dynamic control of multiple metabolic fluxes under complex metabolic background and presents paradigms to engineer metabolic pathways for high-level synthesis of target products.

A novel quorum quencher, Rhodococcus pyridinivorans XN-36, is a powerful agent for the biocontrol of soft rot disease in various host plants

Quorum sensing (QS) is a microbial cell–cell communication mechanism that regulates the virulence factor production in numerous pathogens, which plays a key role in microbial infections. QS-mediated microbial infections can be blocked via quorum quenching (QQ), which disrupts QS either by degradation of QS signals or interference of signal generation or perception. The pathogenicity of various diseases, including Pectobacterium carotovorum, is regulated by N-acyl homoserine lactone (AHL), a widely conserved QS signaling molecule. P. carotovorum can induce soft rot in a variety of crops and cause great economic losses to agricultural production. In this study, a newly isolated bacterium of Rhodococcus pyridinivorans XN-36 was identified as a novel QQ strain that can effectively degrade AHL and reduce the disease severity of P. carotovorum in host plants. Strain XN-36 was capable of rapidly degrading AHL without a lag phase, and over 85% of AHL (0.5 mmol·L−1) was degraded within 96 h. The metabolic intermediates of AHL biodegradation were detected and identified by gas chromatography-mass spectrometry (GC–MS) as lactamide and propenamide. Based on the chemical structure of AHL and intermediate metabolites, a novel metabolic pathway of AHL in strain XN-36 was proposed, which suggests that AHL could be degraded first by cleavage of its amide bond, followed by hydrolysis of the lactonic ring and subsequent metabolism. In addition, strain XN-36 participated in efficient degradation of a wide range of AHL signaling molecules including N-(3-oxohexanoyl)-L-homoserine lactone (OHHL), N-hexanoyl-L-homoserine lactone (C6HSL), N-(3-oxooctanoyl)-L-homoserine lactone (3OC8HSL), and N-(3-oxododecanoyl)-L-homoserine lactone (3OC12HSL). Furthermore, the application of strain XN-36 as a biocontrol agent could substantially alleviate the soft rot disease caused by P. carotovorum to suppress tissue maceration in a variety of host plants, including Chinese cabbage (Brassica pekinensis(Lour.) Rupr.), carrot (Daucus carota L.) and potato (Solanum tuberosum L.). Similarly, the application of crude enzymes of strain XN-36 significantly attenuated the disease incidence and severity in host plants. Enzyme activity test indicated that strain XN-36 has acylase activity. These findings expand the application of QQ strains as biocontrol agents, while opening up new prospects for the control of QS-mediated bacterial diseases.

A dialogue-like cell communication mechanism is conserved in filamentous ascomycete fungi and mediates interspecies interactions

In many filamentous fungi, germinating spores cooperate by fusing into supracellular structures, which develop into the mycelial colony. In the model fungus Neurospora crassa, this social behavior is mediated by an intriguing mode of communication, in which two fusing cells take turns in signal sending and receiving. Here we show that this dialogue-like cell communication mechanism is highly conserved in distantly related fungal species and mediates interspecies interactions. In mixed populations, cells of N. crassa and the phytopathogenic gray mold Botrytis cinerea coordinate their behavior over a spatial distance and establish physical contact. Subsequent cell–cell fusion is, however, restricted to germlings of the same species, indicating that species specificity of germling fusion has evolved not on the level of the signal/receptor but at subsequent levels of the fusion process. In B. cinerea, fusion and infectious growth are mutually exclusive cellular programs. Remarkably, the presence of N. crassa can reprogram this behavior and induce fusion of the gray mold on plant surfaces, potentially weakening its pathogenic potential. In a third fungal species, the nematode-trapping fungus Arthrobotrys flagrans, the conserved signaling mechanism mediates vegetative fusion within mycelial colonies but has also been repurposed for the formation of nematode-catching traps. In summary, this study identified the cell dialogue mechanism as a conserved complex trait and revealed that even distantly related fungi possess a common molecular language, which promotes cellular contact formation across species borders.

Tubular epithelial cell-to-macrophage communication forms a negative feedback loop via extracellular vesicle transfer to promote renal inflammation and apoptosis in diabetic nephropathy.

Background: Macrophage infiltration around lipotoxic tubular epithelial cells (TECs) is a hallmark of diabetic nephropathy (DN). However, how these two types of cells communicate remains obscure. We previously demonstrated that LRG1 was elevated in the process of kidney injury. Here, we demonstrated that macrophage-derived, LRG1-enriched extracellular vesicles (EVs) exacerbated DN.Methods: We induced an experimental T2DM mouse model with a HFD diet for four months. Renal primary epithelial cells and macrophage-derived EVs were isolated from T2D mice by differential ultracentrifugation. To investigate whether lipotoxic TEC-derived EV (EVe) activate macrophages, mouse bone marrow-derived macrophages (BMDMs) were incubated with EVe. To investigate whether activated macrophage-derived EVs (EVm) induce lipotoxic TEC apoptosis, EVm were cocultured with primary renal tubular epithelial cells. Subsequently, we evaluated the effect of LRG1 in EVe by investigating the apoptosis mechanism.Results: We demonstrated that incubation of primary TECs of DN or HK-2 mTECs with lysophosphatidyl choline (LPC) increased the release of EVe. Interestingly, TEC-derived EVe activated an inflammatory phenotype in macrophages and induced the release of macrophage-derived EVm. Furthermore, EVm could induce apoptosis in TECs injured by LPC. Importantly, we found that leucine-rich α-2-glycoprotein 1 (LRG1)-enriched EVe activated macrophages via a TGFβR1-dependent process and that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-enriched EVm induced apoptosis in injured TECs via a death receptor 5 (DR5)-dependent process.Conclusion: Our findings indicated a novel cell communication mechanism between tubular epithelial cells and macrophages in DN, which could be a potential therapeutic target.

Biofilm mediated strategies to mitigate heavy metal pollution: A critical review in metal bioremediation

Mining and various industrial activities, along with generation and accumulation of heavy metals due to agricultural and domestic activities are languishing human health and the environment as a whole. Employment of conventional strategies in eradicating these toxic loads, are way expensive and concerned with the production of secondary wastes. Biofilm being a syntropic microbial consortium, through the mechanism of cell communication and signaling, quorum sensing and modulating strategies accomplish the removal of contaminant metals from environment. Such biofilm mediated bioremediation may be explicitly explained by implementing synthetic biology models and through unique mathematical modelling of mechanisms of multi species biofilm formation and survival strategies in toxic environments. Microbial metabolism for extracellular electron transfer (EET) and development of niche-specific microbial electrochemistry-driven biotechnologies, exploit the bio electrochemical system of electroactive biofilms (EABs) for removal of metal ions from environment. The multi omics platform predicts the pathways of modified metal-biofilm interaction and sequestration strategies as crucial mechanism to accelerate biofilm mediated bioremediation processes.

Making Blood from the Vessel: Extrinsic and Environmental Cues Guiding the Endothelial-to-Hematopoietic Transition.

It is increasingly recognized that specialized subsets of endothelial cells carry out unique functions in specific organs and regions of the vascular tree. Perhaps the most striking example of this specialization is the ability to contribute to the generation of the blood system, in which a distinct population of “hemogenic” endothelial cells in the embryo transforms irreversibly into hematopoietic stem and progenitor cells that produce circulating erythroid, myeloid and lymphoid cells for the lifetime of an animal. This review will focus on recent advances made in the zebrafish model organism uncovering the extrinsic and environmental factors that facilitate hemogenic commitment and the process of endothelial-to-hematopoietic transition that produces blood stem cells. We highlight in particular biomechanical influences of hemodynamic forces and the extracellular matrix, metabolic and sterile inflammatory cues present during this developmental stage, and outline new avenues opened by transcriptomic-based approaches to decipher cell–cell communication mechanisms as examples of key signals in the embryonic niche that regulate hematopoiesis.

3D Cancer Models: Depicting Cellular Crosstalk within the Tumour Microenvironment.

Simple SummaryThe tumour microenvironment is composed of multiple non-cancerous cells that communicate with the tumour cells, influencing their behaviour and impacting the progression of the disease and the response to therapy. To better understand the disease and try to predict the response of patients to therapy, there has been an effort to develop experimental strategies that could represent this complex human tumour microenvironment in a dish (in vitro). In this review, we describe the importance of each cell type and review the in vitro approaches recently developed for cultivating together the different cell types (co-culture) in a three-dimensional configuration to better represent the architecture of the tumour and cell interactions (3D models). We describe and compare the different studies and outline perspectives on the 3D modelling strategies and their potential impact in cancer research and anticancer drug discovery.The tumour microenvironment plays a critical role in tumour progression and drug resistance processes. Non-malignant cell players, such as fibroblasts, endothelial cells, immune cells and others, interact with each other and with the tumour cells, shaping the disease. Though the role of each cell type and cell communication mechanisms have been progressively studied, the complexity of this cellular network and its role in disease mechanism and therapeutic response are still being unveiled. Animal models have been mainly used, as they can represent systemic interactions and conditions, though they face recognized limitations in translational potential due to interspecies differences. In vitro 3D cancer models can surpass these limitations, by incorporating human cells, including patient-derived ones, and allowing a range of experimental designs with precise control of each tumour microenvironment element. We summarize the role of each tumour microenvironment component and review studies proposing 3D co-culture strategies of tumour cells and non-malignant cell components. Moreover, we discuss the potential of these modelling approaches to uncover potential therapeutic targets in the tumour microenvironment and assess therapeutic efficacy, current bottlenecks and perspectives.

Identification of FadT as a Novel Quorum Quenching Enzyme for the Degradation of Diffusible Signal Factor in Cupriavidus pinatubonensis Strain HN-2.

Quorum sensing (QS) is a microbial cell–cell communication mechanism and plays an important role in bacterial infections. QS-mediated bacterial infections can be blocked through quorum quenching (QQ), which hampers signal accumulation, recognition, and communication. The pathogenicity of numerous bacteria, including Xanthomonas campestris pv. campestris (Xcc), is regulated by diffusible signal factor (DSF), a well-known fatty acid signaling molecule of QS. Cupriavidus pinatubonensis HN-2 could substantially attenuate the infection of XCC through QQ by degrading DSF. The QQ mechanism in strain HN-2, on the other hand, is yet to be known. To understand the molecular mechanism of QQ in strain HN-2, we used whole-genome sequencing and comparative genomics studies. We discovered that the fadT gene encodes acyl-CoA dehydrogenase as a novel QQ enzyme. The results of site-directed mutagenesis demonstrated the requirement of fadT gene for DSF degradation in strain HN-2. Purified FadT exhibited high enzymatic activity and outstanding stability over a broad pH and temperature range with maximal activity at pH 7.0 and 35 °C. No cofactors were required for FadT enzyme activity. The enzyme showed a strong ability to degrade DSF. Furthermore, the expression of fadT in Xcc results in a significant reduction in the pathogenicity in host plants, such as Chinese cabbage, radish, and pakchoi. Taken together, our results identified a novel DSF-degrading enzyme, FadT, in C. pinatubonensis HN-2, which suggests its potential use in the biological control of DSF-mediated pathogens.