Intercellular Signaling Research Articles

The extracellular matrix with a continuous gradient of SDF1α guides the oriented migration of human umbilical cord mesenchymal stem cells

The extracellular matrix (ECM) plays a crucial role in maintaining cell morphology and facilitating intercellular signal transmission within the human body. ECM has been extensively utilized for tissue injury repair. However, the consideration of factor gradients during ECM preparation has been limited. In this study, we developed a novel approach to generate sheet-like ECM with a continuous gradient of stromal cell-derived factor-1 (SDF1α). Briefly, we constructed fibroblasts to overexpress SDF1αfused with the collagen-binding domain (CBD-SDF1α), and cultured these cells on a slanted plate to establish a gradual density cell layer at the bottom surface. Subsequently, excess parental fibroblasts were evenly distributed on the plate laid flat to fill the room between cells. Following two weeks of culture, the monolayer cells were lyophilized to form a uniform ECM sheet possessing a continuous gradient of SDF1α. This engineered ECM material demonstrated its ability to guide oriented migration of human umbilical cord mesenchymal stem cells on the ECM sheet. Our simple yet effective method holds great potential for advancing research in regenerative medicine.

Sinusoidal communication in chronic liver disease.

The liver sinusoid, mainly composed of liver sinusoidal endothelial cells, hepatic macrophages and hepatic stellate cells, shapes the hepatic vasculature and is key maintaining liver homeostasis and function. During chronic liver disease (CLD), the function of sinusoidal cells is impaired, being directly involved in the progression of liver fibrosis, cirrhosis, and main clinical complications including portal hypertension and hepatocellular carcinoma. In addition to their roles in liver diseases pathobiology, sinusoidal cells' paracrine communication or cross-talk is being studied as a mechanism of disease but also as a remarkable target for treatment. The aim of this review is to gather current knowledge of intercellular signalling in the hepatic sinusoid during the progression of liver disease. We summarise studies developed in pre-clinical models of CLD, specially emphasizing those pathways characterized in human-based clinically relevant models. Finally, we describe pharmacological treatments targeting sinusoidal communication as promising options to treat CLD and its clinical complications.

Pancreatic cancer is feeling the heat.

Pancreatic adenocarcinoma (PDAC) is considered an immunologically 'cold' tumor that fails to attract or support effector T cells. Most PDACs are resistant to immune checkpoint blockade due to the complex signaling pathways that exist within its tumor microenvironment. Recent advances in genomic and proteomic technology advances are finally uncovering the complex inflammatory cellular and intercellular signals that require modulation and reprogramming. The goal is to 'turn up the heat' on PDACs with combination immunotherapies that incorporate T cell activating agents and immune modulatory agents, and successfully eradicate tumors. Here, we discuss progress and promising new research that is moving the field toward this goal.

EphA-Mediated Regulation of Stomatin Expression in Prostate Cancer Cells.

Tumor growth and progression are affected by interactions between tumor cells and stromal cells within the tumor microenvironment. We previously showed that the expression of an integral membrane protein, called stomatin, was increased in cancer cells following their association with stromal cells. Additionally, stomatin impaired the Akt signaling pathway to suppress tumor growth. However, it remains unclear how stomatin expression is regulated. To explore this, we examined the cell surface molecules that can transduce the intercellular communication signals between cancer cells and stromal cells. Among these molecules, EphA3 and EphA7 receptors and their ligand ephrin-A5 were found to be expressed in prostate cancer cells, but not in prostate stromal cells. Cell-to-cell contact of prostate cancer cells through the EphA-ephrin-A interaction suppressed stomatin expression, while knockdown of EphA3/7 or ephrin-A5 increased stomatin expression. This increase contributed to an inhibition of prostate cancer cell proliferation. Intracellularly, the binding of ephrin-A to EphA attenuated extracellular signaling-regulated kinase (ERK) activation that promoted stomatin expression. Furthermore, ELK1 and ELK4, which are Ets family transcription factors phosphorylated by ERK, were involved in the induction of stomatin expression. We also found that higher Gleason score prostate cancer tissue samples had increased activation of EphA, while the stomatin expression and activated ERK and ELK levels were all low. In the mouse xenograft tumor samples generated by implantation of prostate cancer cells, EphA3 phosphorylation was attenuated and the ERK-ELK signaling and stomatin expression were enhanced in the area where stromal cells infiltrated the tumor. The EphA-mediated signaling suppresses the ERK-ELK pathway, leading to the reduction of stomatin expression that affects prostate cancer malignancy.

Achilles tendinopathy treatment via circadian rhythm regulation

IntroductionAchilles tendinopathy (AT) is a prevalent musculoskeletal disorder closely linked to oxidative stress. Existing evidence suggests a potential link between circadian clock rhythms and oxidative stress. However, the precise role of the circadian clock in the progression and treatment of AT remains unclear. ObjectiveThe purpose of this study was to investigate the role of the Achilles tendon circadian clock in AT pathology and explore the potential use of biomaterials for modulating the circadian clock in the treatment of AT. MethodsWe utilized in vivo and in vitro models to investigate the alterations of the circadian clock within the Achilles tendon during the progression of AT, as well as its impact on disease development. Additionally, we fabricated Nb2C@CeO2 composites featuring a Schottky heterojunction for regulating the circadian rhythm and validated its therapeutic efficacy and molecular mechanism of AT through both in vivo and in vitro experiments. ResultsThe Achilles tendon functioned as a peripheral oscillator with an independent and self-sustained time-keeping system. The rhythm of the Achilles tendon clock was disrupted during the development of AT, as indicated by the decreased amplitude of Bmal1 and Nrf2 rhythm expression. Mechanistically, the knockdown of Bmal1 disrupted the Achilles tendon clock, thereby destroying the Bmal1-Nrf2 axis dependent molecular defense mechanism, and exacerbating the inflammatory response, whereas overexpression of Bmal1 had a protective effect. Nb2C@CeO2 composites with Schottky heterojunctions enhance intercellular electrical signaling, boosting Bmal1 expression and mitigating AT’s pathological changes. Importantly, enhancing Bmal1 expression during its peak, rather than its trough, was more effective. ConclusionThis study identified the protective role of the circadian clock against oxidative stress and inflammation in the Achilles tendon. Achilles tendon circadian clock-targeted therapy represents a promising strategy for AT treatment.

The critical involvement of monocytes/macrophages in the pathogenesis of primary Sjögren's syndrome: New evidence from Mendelian randomization and single-cell sequencing

BackgroundPrimary Sjögren's syndrome (pSS) stands as a chronic autoimmune disease characterized by an elusive pathogenesis. The synergy of single-cell RNA sequencing and Mendelian randomization (MR) analysis provides an opportunity to comprehensively unravel the contributory role of monocytes/macrophages in the intricate pathogenesis of pSS. MethodsDifferentially expressed genes (DEGs) of various types of immune cells were analyzed after annotating single-cell RNA sequencing (scRNA-seq) data. MR analysis of expression quantitative trait loci (eQTL) and protein quantitative trait loci (pQTL) was conducted to search for key pathogenic genes and proteins. Cellular localization of pathogenic genes was performed based on scRNA-seq data. Variations in signaling pathways between immune cells were further analyzed. ResultsA total of 1434 significant DEGs were identified. Among these, 60 genes exhibited strong relevance to the occurrence of pSS, of which 32 genes differentially expressed in monocytes/macrophages. CTSS was found to be a significant risk protein with a p-value of 0.001 and an odds ratio of 1.384 (1.147–1.669), showing pronounced expression in monocytes/macrophages. Furthermore, monocytes/macrophages displayed heightened expression levels of MXD1, AMPD2, TNFSF10, FTL, UBXN11, CSF3R, and LILRA5. The analysis of intercellular signaling revealed increased signal intensity in both incoming and outgoing signals in monocytes/macrophages. The signaling interactions between monocytes/macrophages, B cells, and T cells exhibited varying degrees of deviation. ConclusionsThis study highlights the significant involvement of monocytes/macrophages in the pathogenesis of pSS, as evidenced by MR analysis and scRNA-seq analysis. This suggests monocytes/macrophages as a focal point for pathogenesis research and potential therapeutic targeting in pSS.

Evolution, Gene Duplication, and Expression Pattern Analysis of CrRLK1L Gene Family in Zea mays (L.).

Catharanthus roseus receptor-like kinase 1-like (CrRLK1L) plays pivotal roles in regulating plant growth and development, mediating intercellular signal transduction, and modulating responses to environmental stresses. However, a comprehensive genome-wide identification and analysis of the CrRLK1L gene family in maize remains elusive. In this study, a total of 24 CrRLK1L genes were identified in the maize whole genome. A phylogenetic analysis further revealed that CrRLK1L proteins from Arabidopsis, rice, and maize were grouped into nine distinct subgroups, with subgroup IV being unique to maize. Gene structure analysis demonstrated that the number of introns varied greatly among ZmCrRLK1L genes. Notably, the genome-wide duplication (WGD) events promoted the expansion of the ZmCrRLK1L gene family. Compared with Arabidopsis, there were more collinear gene pairs between maize and rice. Tissue expression patterns indicated that ZmCrRLK1L genes are widely expressed in various tissues, with ZmCrRLK1L5/9 specifically highly expressed in roots, and ZmCrRLK1L8/14/16/21/22 expressed in anthers. Additionally, RNA-seq and RT-qPCR analyses revealed that the expression of ZmCrRLK1L1/2/20/22 genes exhibited different expression patterns under drought and salt stresses. In summary, our study lays a foundation for elucidating the biological roles of ZmCrRLK1L genes in maize growth and development, reproductive development, and stress responses.

CD44 facilitates adhesive interactions in airineme-mediated intercellular signaling.

Specialized cellular protrusions facilitate local intercellular communications in various species, including mammals. Among these, airinemes play a crucial role in pigment pattern formation in zebrafish by mediating long-distance Notch signaling between pigment cells. Remarkably, airinemes exhibit large vesicle-like structure at their tips, which are pulled by macrophages and delivered to target cells. The interaction between macrophages and Delta-ligand carrying airineme vesicles is essential for initiating airineme-mediated signaling, yet the molecular detail of this interaction remains elusive. Through high-resolution live imaging, genetic in vivo manipulations and in vitro adhesion assay, we found that adhesive interactions via the extracellular domain of CD44, a class I transmembrane glycoprotein, between macrophages and airineme vesicles are critical for airineme signaling. Mutants lacking the extracellular domain of CD44 lose their adhesiveness, resulting in a significant reduction in airineme extension and pigment pattern defects. Our findings provide valuable insights into the role of adhesive interactions between signal-sending cells and macrophages in a long-range intercellular signaling.

Spatiotemporal Control Over Protein Release from Artificial Cells via a Light-Activatable Protease.

The regulation of protein uptake and secretion by cells is paramount for intercellular signaling and complex multicellular behavior. Mimicking protein-mediated communication in artificial cells holds great promise to elucidate the underlying working principles, but remains challenging without the stimulus-responsive regulatory machinery of living cells. Therefore, systems to precisely control when and where protein release occurs should be incorporated in artificial cells. Here, a light-activatable TEV protease (LaTEV) is presented that enables spatiotemporal control over protein release from a coacervate-based artificial cell platform. Due to the presence of Ni2+-nitrilotriacetic acid moieties within the coacervates, His-tagged proteins are effectively sequestered into the coacervates. LaTEV is first photocaged, effectively blocking its activity. Upon activation by irradiation with 365nm light, LaTEV cleaves the His-tags from sequestered cargo proteins, resulting in their release. The successful blocking and activation of LaTEV provides control over protein release rate and triggerable protein release from specific coacervates via selective irradiation. Furthermore, light-activated directional transfer of proteins between two artificial cell populations is demonstrated. Overall, this system opens up avenues to engineer light-responsive protein-mediated communication in artificial cell context, which can advance the probing of intercellular signaling and the development of protein delivery platforms.

Induced Pluripotent Stem Cell-Derived Parathyroid Organoids Resemble Parathyroid Morphology and Function.

The primary role of the parathyroid glands is to maintain calcium homeostasis through the secretion of parathyroid hormone (PTH). The limited proliferative capacity and differentiation of parathyroid cells hinder the generation of cell therapy options. In this study, parathyroid organoids are successfully generated from human-induced pluripotent stem cells (hiPSCs). At the end of the 20 days of differentiation, the parathyroid organoids exhibited distinct parathyroid morphology. Stereomicroscope, scanning electron microscopy (SEM), and transmission electron microscopy (TEM) analysis demonstrated the 3D arrangement of the cell layers in which intracellular structures of parathyroid cells resemble human parathyroid cellular morphology. Comprehensive molecular analyses, including RNA sequencing (RNA-Seq) and liquid chromatography/mass spectrometry (LC-MS/MS), confirmed the expression of key parathyroid-related markers. Protein expression of CasR, CxCr4, Gcm2, and PTH are observed in parathyroid organoids. Parathyroid organoids secrete PTH, demonstrate active intercellular calcium signaling, and induce osteogenic differentiation via their secretome. The tissue integration potential of parathyroid organoids is determined by transplantation into parathyroidectomized rats. The organoid transplanted animals showed significant elevations in PTH-related markers (CasR, CxCr4, Foxn1, Gcm2, and PTH). PTH secretion is detected in organoid-transplanted animals. The findings represent a significant advancement in parathyroid organoid culture and may offer a cellular therapy for treating PTH-related diseases, including hypoparathyroidism.

Tumor Cell Communications as Promising Supramolecular Targets for Cancer Chemotherapy: A Possible Strategy

Fifty-two years have passed since President Nixon launched the “War on Cancer”. Despite unparalleled efforts and funds allocated worldwide, the outlined goals were not achieved because cancer treatment approaches such as chemotherapy, radiation therapy, hormonal and targeted therapies have not fully met the expectations. Based on the recent literature, a new direction in cancer therapy can be proposed which targets connections between cancer cells and their microenvironment by chemical means. Cancer–stromal synapses such as immunological synapses between cancer and immune cells provide an attractive target for this approach. Such synapses form ligand–receptor clusters on the interface of the interacting cells. They share a common property of involving intercellular clusters of spatially proximate and cooperatively acting proteins. Synapses provide the space for the focused intercellular signaling molecules exchange. Thus, the disassembly of cancer–stromal synapses may potentially cause the collapse of various tumors. Additionally, the clustered arrangement of synapse components offers opportunities to enhance treatment safety and precision by using targeted crosslinking chemical agents which may inactivate cancer synapses even in reduced concentrations. Furthermore, attaching a cleavable cell-permeable toxic agent(s) to a crosslinker may further enhance the anti-cancer effect of such therapeutics. The highlighted approach promises to be universal, relatively simple and cost-efficient. We also hope that, unlike chemotherapeutic and immune drugs that interact with a single target, by using supramolecular large clusters that include many different components as a target, the emergence of a resistance characteristic of chemo- and immunotherapy is extremely unlikely.

Low-affinity ligands of the epidermal growth factor receptor are long-range signal transmitters during collective cell migration of epithelial cells.

Epidermal growth factor receptor ligands (EGFRLs) consist of seven proteins. In stark contrast to the amassed knowledge concerning the epidermal growth factor receptors themselves, the extracellular dynamics of individual EGFRLs remain elusive. Here, employing fluorescent probes and a tool for triggering ectodomain shedding of EGFRLs, we show that EREG, a low-affinity EGFRL, exhibits the most rapid and efficient activation of EGFR in confluent epithelial cells and mouse epidermis. In Madin-Darby canine kidney (MDCK) renal epithelial cells, EGFR- and ERK-activation waves propagate during collective cell migration in an ADAM17 sheddase- and EGFRL-dependent manner. Upon induction of EGFRL shedding, radial ERK activation waves were observed in the surrounding receiver cells. Notably, the low-affinity ligands EREG and AREG mediated faster and broader ERK waves than the high-affinity ligands. The integrity of tight/adherens junctions was essential for the propagation of ERK activation, implying that the tight intercellular spaces prefer the low-affinity EGFRL to the high-affinity ligands for efficient signal transmission. To validate this observation in vivo , we generated EREG-deficient mice expressing the ERK biosensor and found that ERK wave propagation and cell migration were impaired during skin wound repair. In conclusion, we have quantitatively demonstrated the distinctions among EGFRLs in shedding, diffusion, and target cell activation in physiological contexts. Our findings underscore the pivotal role of low-affinity EGFRLs in rapid intercellular signal transmission.

Dysfunction of Endothelial Cell-Mediated Intercellular Communication and Metabolic Pathways in Age-Related Macular Degeneration

Purpose Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, but the therapies are not satisfactory. This study aimed to find AMD specific features through the analysis of high-throughput sequencing. Methods In this study, we integrated six projects containing single-cell RNA sequencing (scRNA-seq) data to perform a comprehensive analysis for AMD samples in the tissues of retina and retinal pigment epithelium/choroid, and in the positions of macula and periphery. Differentially expressed genes (DEGs) were analyzed and crucial signaling pathways were identified across cell types and between the macula and periphery. The intercellular signaling transduction among cell types were inferred by "CellChat" to build cell–cell communication network under normal and AMD conditions, and verified at the transcriptional level. The CD31+ endothelial cells were obtained to evaluate the enrichment of KEGG pathways in atrophic and neovascular AMD, and GSVA was adopted to discover differential metabolic signals in each AMD type. Results Thirteen major cell types were identified in the integrated scRNA-seq data. Although no disease-specific cell type or differential cell proportion was found, DEGs and enriched pathways were shown in cell-type- and position-dependent manners. Severe impairment of endothelial cell-mediated cell interactions was found in the signaling transduction network of the macula, and compromised cell interactions were observed in the periphery. Furthermore, distinct signaling pathways and metabolic states were uncovered in atrophic and neovascular AMD. Striking reduction in energy metabolism, lipid metabolism, and oxidative stress was indicated in the atrophic AMD. Conclusion Conclusively, we discover aberrant signals and metabolic pathways in AMD samples, providing insight into mechanisms and potential therapeutic targets for the AMD treatment.

Blood Products and Stem Cells in Osteoarthritis Therapy

The principle of regenerative medicine in the treatment of osteoarthritis pursues a functional restoration of cartilage tissue instead of just repairing cartilage defects. The use of blood products is intended to inhibit chronic inflammatory processes and promote tissue regeneration. Intraarticular injection of autologous platelet-rich plasma (PRP) is a prominent procedure. Clinical evidence supports PRP injection over hyaluronic acid or glucocorticoid injection. Comparability of studies is difficult due to missing standardisation of production procedures, dosing and donor variability. In particular, whether presence of residual leukocytes is required or should be avoided is an open debate. In contrast, stem cell therapies in osteoarthritis therapy are often based on mesenchymal stem cells (MSC) from adipose tissue or bone marrow aspirate. Different sources of MSC might render the cells more suitable for application in a given context. Nevertheless, it became evident that their secretome rather than the cells themselves are responsible for observed regenerative processes. Research on the mechanisms of action have focused on growth factors. However, an overlooked component of blood products called extracellular vesicles (EV) came to the center of attention, which are also released by MSC as intercellular signal carriers. EV cargo molecules such as miRNAs open up new dimensions in the investigation and explanation of clinically observed anti-inflammatory and regenerative effects.

Mast cells as indicators of foreign particle biocompatibility

The key problem of introducing nanoparticles into clinical practice for diagnostic and therapeutic purposes is their safety. Connective tissue, an important component of which are mast cells, reacts actively in response to foreign particles. The reaction of mast cells can be an indicator of the biocompatibility of foreign particles. The study was conducted on male Wistar rats. Iron-carbon nanoparticles in the FeC modification stabilized in an aqueous medium using an auxiliary substance were used. Tissue examination (liver, lungs, heart, thymus, kidneys) was performed 1, 7 and 30 days after injection. After the injection of nanoparticles, the largest quantity of them is found in the liver and lungs, a smaller quantity is found in the heart, kidneys and thymus. The liver and lungs are the main organs of excretion of nanoparticles due to phagocytes. The accumulation of nanoparticles in the liver leads to the development of destructive processes and to the activation of compensatory and adaptive mechanisms in the form of cellular and intracellular regeneration of hepatocytes. In organs with a low content of nanoparticles, structural changes are poorly expressed. The mast cells of the studied organs react differently to the introduction of nanoparticles. The first to react are the mast cells of the liver by reducing the quantity and increasing degranulation. The population of lung mast cells reacts unidirectionally by sharply activating degranulation without changing the amount. An increase in the secretory activity of mast cells in the lungs and liver indicates the participation of mast cells in the regulation of particle elimination through intercellular signaling pathways of interaction with the system of phagocytic mononuclear cells. Heart mast cells are involved in maintaining the inflammatory process in the early period of the experiment, contribute to the return of myocardial parameters to homeostatic norm in the late period of the experiment. Mast cells can be considered as indicators of biocompatibility nanoparticles. The absence of an inflammatory process and the preservation of the structural and functional characteristics of the tissues where nanoparticles accumulate, as well as the reaction of mast cells in them, indicate the relative safety of the particles under study.

New perspectives on the role of platelet factors in enhancing wound regeneration

Aim. To analyze the use of biological factors in the stimulation of the wound healing process. In the course of the study, we analysed relevant domestic and foreign literature sources on the given topic.Methods. The literature was reviewed using the key query ‘the role of biological factors in wound healing stimulation’ through the eLIBRARY and PubMed databases.Results. Currently, the range of therapeutic approaches is broad and diverse, incorporating both traditional and experimental methods such as advanced dressings, tissue matrices, growth factors (GFs), cell therapy, and nanotechnology. The wound healing process is regulated by a complex interplay of intercellular, intracellular, and extracellular signalling mechanisms across various phases of healing.Conclusion. The application of platelet-based therapies in different medical fields has shown promising outcomes in certain conditions, such as acute and chronic injuries of bone and cartilage. However, platelet-based preparations have yet to gain widespread clinical use. Several studies have demonstrated the involvement of platelets and related products, such as platelet microparticles (PMPs) and exosomes, in multiple phases of wound healing. The presence of a substantial number of biologically active molecules within platelet granules—exhibiting anti-inflammatory, angiogenic, proliferative, and other properties—renders platelets particularly attractive for use in regenerative medicine, including the stimulation of wound healin

Circulating Exosomal miRNA Profiles in Non-Small Cell Lung Cancers.

A growing number of studies have shown that microRNAs (miRNAs) can exert oncogenic or tumor suppressor activities in a variety of cancers, including lung cancer. Given their presence in exosome preparations, microRNA molecules may in fact participate in exosomal intercellular transfers and signaling. In the present study, we examined the profile of 25 circulating exosomal microRNAs in ostensibly healthy controls compared to patients with squamous cell lung cancers (SQCLC) or lung adenocarcinomas (LUAD). Eight miRNAs, namely, miR-21-5p, miR-126-3p, miR-210-3p, miR-221-3p, Let-7b-5p, miR-146a-5p, miR-222-3p, and miR-9-5p, were highly enriched in the cohort and selected for further analyses. All miRNAs were readily detected in non-small cell lung cancer (NSCLC) patients of both sexes at all cancer stages, and their levels in exosomes correlated with the clinicopathological characteristics of tumors. Thus, the presence of these miRNAs in circulating exosomes may contribute to the regulation of oncogenic activity in patients with NSCLC.

CollectNET: a web server for integrated inference of cell-cell communication network.

Cell-cell communication (CCC) through ligand-receptor (L-R) pairs forms the cornerstone for complex functionalities in multicellular organisms. Deciphering such intercellular signaling can contribute to unraveling disease mechanisms and enable targeted therapy. Nonetheless, notable biases and inconsistencies are evident among the inferential outcomes generated by current methods for inferring CCC network. To fill this gap, we developed collectNET (http://health.tsinghua.edu.cn/collectnet) as a comprehensive web platform for analyzing CCC network, with efficient calculation, hierarchical browsing, comprehensive statistics, advanced searching, and intuitive visualization. collectNET provides a reliable online inference service with prior knowledge of three public L-R databases and systematic integration of three mainstream inference methods. Additionally, collectNET has assembled a human CCC atlas, including 126 785 significant communication pairs based on 343 023 cells. We anticipate that collectNET will benefit researchers in gaining a more holistic understanding of cell development and differentiation mechanisms. Database URL: http://health.tsinghua.edu.cn/collectnet.

CellChat for systematic analysis of cell-cell communication from single-cell transcriptomics.

Recent advances in single-cell sequencing technologies offer an opportunity to explore cell-cell communication in tissues systematically and with reduced bias. A key challenge is integrating known molecular interactions and measurements into a framework to identify and analyze complex cell-cell communication networks. Previously, we developed a computational tool, named CellChat, that infers and analyzes cell-cell communication networks from single-cell transcriptomic data within an easily interpretable framework. CellChat quantifies the signaling communication probability between two cell groups using a simplified mass-action-based model, which incorporates the core interaction between ligands and receptors with multisubunit structure along with modulation by cofactors. Importantly, CellChat performs a systematic and comparative analysis of cell-cell communication using a variety of quantitative metrics and machine-learning approaches. CellChat v2 is an updated version that includes additional comparison functionalities, an expanded database of ligand-receptor pairs along with rich functional annotations, and an Interactive CellChat Explorer. Here we provide a step-by-step protocol for using CellChat v2 on single-cell transcriptomic data, including inference and analysis of cell-cell communication from one dataset and identification of altered intercellular communication, signals and cell populations from different datasets across biological conditions. The R implementation of CellChat v2 toolkit and its tutorials together with the graphic outputs are available at https://github.com/jinworks/CellChat . This protocol typically takes ~5 min depending on dataset size and requires a basic understanding of R and single-cell data analysis but no specialized bioinformatics training for its implementation.

Exploring the Insights on Exosomes and their Utility in Treating Ophthalmic Disease: Delving into the Clinical Approval and Present Trials.

Ophthalmic diseases include a wide array of conditions, each requiring individualized treatment approaches. In ophthalmic research and as therapeutics against potential pharmacological indications, several subtypes of exosomes (EVs) have been reconnoitered, mainly for their regenerative, neuroprotective, and anti-inflammatory characteristics. EVs are recently gaining wider attention as promising vehicles for therapies because of their natural participation in communication between cells and targeted delivery. These small vesicles, derived from cells, transport numerous molecules between cells, thus contributing advantages like low immunogenicity, stability, and the ability to target cells specifically. These inherent advantages of carrying the therapeutic cargo and enabling intercellular signaling make them a captivating avenue for progressing ophthalmic disease treatment options. While research is ongoing, and clinical applications are still emerging, several EV subtypes have shown promise for possible applications in addressing several ophthalmic diseases, such as glaucoma, age-related macular degenerative disorders, retinal degenerative disorders, and ocular inflammatory conditions.