Meiosis is a highly complex process significantly influenced by transcriptional regulation.However,studies on the mechanisms that govern transcriptomic changes during meiosis,especially in prophase I,are limited.Here,...Meiosis is a highly complex process significantly influenced by transcriptional regulation.However,studies on the mechanisms that govern transcriptomic changes during meiosis,especially in prophase I,are limited.Here,we performed single-cell ATAC-seq of human testis tissues and observed reprogramming during the transition from zygotene to pachytene spermatocytes.This event,conserved in mice,involved the deactivation of genes associated with meiosis after reprogramming and the activation of those related to spermatogenesis before their functional onset.Furthermore,we identified 282 transcriptional regulators(TRs)that underwent activation or deactivation subsequent to this process.Evidence suggested that physical contact signals from Sertoli cells may regulate these TRs in spermatocytes,while secreted ENHO signals may alter metabolic patterns in these cells.Our results further indicated that defective transcriptional reprogramming may be associated with non-obstructive azoospermia(NOA).This study revealed the importance of both physical contact and secreted signals between Sertoli cells and germ cells in meiotic progression.展开更多
BACKGROUND Liver cancer is one of the deadliest malignant tumors worldwide.Immunotherapy has provided hope to patients with advanced liver cancer,but only a small fraction of patients benefit from this treatment due t...BACKGROUND Liver cancer is one of the deadliest malignant tumors worldwide.Immunotherapy has provided hope to patients with advanced liver cancer,but only a small fraction of patients benefit from this treatment due to individual differences.Identifying immune-related gene signatures in liver cancer patients not only aids physicians in cancer diagnosis but also offers personalized treatment strategies,thereby improving patient survival rates.Although several methods have been developed to predict the prognosis and immunotherapeutic efficacy in patients with liver cancer,the impact of cell-cell interactions in the tumor microenvir-onment has not been adequately considered.AIM To identify immune-related gene signals for predicting liver cancer prognosis and immunotherapy efficacy.METHODS Cell grouping and cell-cell communication analysis were performed on single-cell RNA-sequencing data to identify highly active cell groups in immune-related pathways.Highly active immune cells were identified by intersecting the highly active cell groups with B cells and T cells.The significantly differentially expressed genes between highly active immune cells and other cells were subsequently selected as features,and a least absolute shrinkage and selection operator(LASSO)regression model was constructed to screen for diagnostic-related features.Fourteen genes that were selected more than 5 times in 10 LASSO regression experiments were included in a multivariable Cox regression model.Finally,3 genes(stathmin 1,cofilin 1,and C-C chemokine ligand 5)significantly associated with survival were identified and used to construct an immune-related gene signature.RESULTS The immune-related gene signature composed of stathmin 1,cofilin 1,and C-C chemokine ligand 5 was identified through cell-cell communication.The effectiveness of the identified gene signature was validated based on experi-mental results of predictive immunotherapy response,tumor mutation burden analysis,immune cell infiltration analysis,survival analysis,and expression analysis.CONCLUSION The findings suggest that the identified gene signature may contribute to a deeper understanding of the activity patterns of immune cells in the liver tumor microenvironment,providing insights for personalized treatment strategies.展开更多
Dorsal root ganglion neurons transmit peripheral somatic information to the central nervous system,and dorsal root ganglion neuron excitability affects pain perception.Dorsal root ganglion stimulation is a new approac...Dorsal root ganglion neurons transmit peripheral somatic information to the central nervous system,and dorsal root ganglion neuron excitability affects pain perception.Dorsal root ganglion stimulation is a new approach for managing pain sensation.Knowledge of the cell-cell communication among dorsal root ganglion cells may help in the development of new pain and itch management strategies.Here,we used the single-cell RNA-sequencing(scRNA-seq)database to investigate intercellular communication networks among dorsal root ganglion cells.We collected scRNA-seq data from six samples from three studies,yielding data on a total of 17,766 cells.Based on genetic profiles,we identified satellite glial cells,Schwann cells,neurons,vascular endothelial cells,immune cells,fibroblasts,and vascular smooth muscle cells.Further analysis revealed that eight types of dorsal root ganglion neurons mediated proprioceptive,itch,touch,mechanical,heat,and cold sensations.Moreover,we predicted several distinct forms of intercellular communication among dorsal root ganglion cells,including cell-cell contact,secreted signals,extracellular matrix,and neurotransmitter-mediated signals.The data mining predicted that Mrgpra3-positive neurons robustly express the genes encoding the adenosine Adora2b(A2B)receptor and glial cell line-derived neurotrophic factor family receptor alpha 1(GFRα-1).Our immunohistochemistry results confirmed the coexpression of the A2B receptor and GFRα-1.Intrathecal injection of the A2B receptor antagonist PSB-603 effectively prevented histamine-induced scratching behaviour in a dose-dependent manner.Our results demonstrate the involvement of the A2B receptor in the modulation of itch sensation.Furthermore,our findings provide insight into dorsal root ganglion cell-cell communication patterns and mechanisms.Our results should contribute to the development of new strategies for the regulation of dorsal root ganglion excitability.展开更多
Cell-cell and cell-matrix signaling and communication between adhesion sites involve mechanisms which are required for cellular functions during normal development and homeostasis; however these cellular functions and...Cell-cell and cell-matrix signaling and communication between adhesion sites involve mechanisms which are required for cellular functions during normal development and homeostasis; however these cellular functions and mechanisms are often deregulated in cancer. Aberrant signaling at cell-cell and cell-matrix adhesion sites often involves downstream mediators including Rho GTPases and tyrosine kinases. This review discusses these molecules as putative mediators of cellular crosstalk between cell-cell and cell-matrix adhesion sites, in addition to their attractiveness as therapeutic targets in cancer. Interestingly, inter-junctional crosstalk mechanisms are frequently typified by the way in which bacterial and viral pathogens opportunistically infect or intoxicate mammalian cells. This review therefore also discusses the concept of learning from pathogen-host interaction studies to better understand coordinated communication between cell-cell and cell-matrix adhesion sites, in addition to highlighting the potential therapeutic usefulness of exploiting pathogens or their products to tap into inter-junctional crosstalk. Taken together, we feel that increased knowledge around mechanisms of cell-cell and cell-matrix adhesion site crosstalk and consequently a greater understanding of their therapeutic targeting offers a unique opportunity to contribute to the emerging molecular revolution in cancer biology.展开更多
Mechanobiology has been a highly recognized field in studying the importance of physical forces in physiologies at the molecular,cellular,tissue,organ and body-levels.Beside the intensive work focusing on the fine loc...Mechanobiology has been a highly recognized field in studying the importance of physical forces in physiologies at the molecular,cellular,tissue,organ and body-levels.Beside the intensive work focusing on the fine local biomechanical forces,the long-range force which can propagate through a relatively distant scale(in hundreds of micrometers and beyond)has been an intriguing topic with increasing attentions in recent years.The collective functions at cell population level often rely on cell-cell communications with or without direct contacts.Recent progresses including our own work indicate that the long-range biomechanical force propagating across scales far beyond single cell size may reserve the capability to trigger coordinative biological responses within cell population.Whether and how cells communicate mechanically in a distant manner remains largely to be explored.In respiratory system,the mechanical property of airway smooth muscle(ASM)is associated with asthma attack with prolonged contraction during airway hyper-responsiveness.In this work,we found that ASM cells rapidly self-assembled into a well-constructed network on 3D matrigel containing type I collagen(COL I),which required the collective functions and coordination of thousands of cells completed within 12-16 hours.Cells were assembled with aligned actin stress fibers and elongated nuclei.The assembling process relied on the long-range mechanical forces across the matrix to direct cell-cell distant interactions.We further found that single ASM cells could rapidly initiate multiple buds precisely pointing to neighboring cells in distance,which relied on cell traction force and force strain on the matrix.Beads tracking assay demonstrated the long-range transmission of cellular traction force to distant locations,and modeling of maximum strain distribution on matrix by finite element method predicted the consistency with cell directional protrusions and movements in experiments.Cells could sense each other in distance to move directionally on both non-fibrous matrigel and in much more efficient way when containing COL I.Cells recruited COL I from the hydrogel to build nearly identical COL I fibrous network to mechanically stabilize the cell network.Our results revealed that ASM cells can sense the traction strain transmitted through matrix to initiate distant communications and rapidly coordinate the network assembly at the population level through active cell-matrix interactions.As an interesting phenomenon,cells sound able to’make phone call’via the role of long-range mechanical force.In summary,this work demonstrated that long-range biomechanical force facilitates the collective functions of ASM cell population for network assembly.The cells reacted to traction strain on the matrix for distant communications,which resulted in directional budding and movement.Fibrous COL I had important roles in facilitating the efficiency of force transmission to induce the assembly and stabilizing the cell network.This work has helped advance the understanding of the feature andfunction of long-range biomechanical force at the cell population level.The observed high mechano-sensitivity of ASM cells might suggest a re-enforced feedback of enhanced contraction by excessive ASM under asthmatic condition.展开更多
Tumor-initiating cells(TICs)or cancer stem cells are believed to be responsible for gastrointestinal tumor initiation,progression,metastasis,and drug resistance.It is hypothesized that gastrointestinal TICs(giTICs)mig...Tumor-initiating cells(TICs)or cancer stem cells are believed to be responsible for gastrointestinal tumor initiation,progression,metastasis,and drug resistance.It is hypothesized that gastrointestinal TICs(giTICs)might originate from cell-cell fusion.Here,we systemically evaluate the evidence that supports or opposes the hypothesis of giTIC generation from cell-cell fusion both in vitro and in vivo.We review giTICs that are capable of initiating tumors in vivo with 5000 or fewer in vivo fused cells.Under this restriction,there is currently little evidence demonstrating that giTICs originate from cell-cell fusion in vivo.However,there are many reports showing that tumor generation in vitro occurs with more than 5000 fused cells.In addition,the mechanisms of giTIC generation via cell-cell fusion are poorly understood,and thus,we propose its potential mechanisms of action.We suggest that future research should focus on giTIC origination from cell-cell fusion in vivo,isolation or enrichment of giTICs that have tumor-initiating capabilities with 5000 or less in vivo fused cells,and further clarification of the underlying mechanisms.Our review of the current advances in our understanding of giTIC origination from cell-cell fusion may have significant implications for the understanding of carcinogenesis and future cancer therapeutic strategies targeting giTICs.展开更多
Mechanical stiffness is recognized as a key physical factor and directs cell function via a mechanotransduction process,from extracellular physical cues to intracellular signaling cascades that affect transcriptional ...Mechanical stiffness is recognized as a key physical factor and directs cell function via a mechanotransduction process,from extracellular physical cues to intracellular signaling cascades that affect transcriptional activity.Cells continually receive mechanical signals from both the surrounding matrix and adjacent cells.However,how mechanical stiffness cue at cell-substrate interfaces coordinates cell-cell junctions in guiding mesenchymal stem cell behaviors is poorly understood.Here,polydimethylsiloxane substrates with different stiffnesses were used to study mechanosensation/transduction mechanisms in controlling odontogenic differentiation of dental papilla cells(DPCs).DPC phenotypes(morphology and differentiation)changed in response to the applied force derived from stiff substrates.Significantly,higher expression of paxillin on stiffer substrates promoted DPC dentinogenesis.Upon treatment with siRNA to knockdown paxillin,N-cadherin increased mainly in the cytomembrane at the area of cell-cell contacts,whereasβ-catenin decreased in the nuclei.The result of a double luciferase reporter assay showed that stiffness promotedβ-catenin binding to TCF,which could coactivate the target genes associated with odontogenic differentiation,as evidenced by bioinformatics analysis.Finally,we determined that the addition of aβ-catenin inhibitor suppressed DPC mineralization in all the stiffness groups.Thus,our results indicated that a mechanotransduction process from cell-substrate interactions to cell-cell adhesions was required for DPC odontogenic differentiation under the stimulation of substrate stiffness.This finding suggests that stem cell fate specification under the stimulus of stiffness at the substrates is based on crosstalk between substrate interactions and adherens junctions,which provides an essential mechanism for cell-based tissue engineering.展开更多
A small proportion of mononuclear diploid cardiomyocytes(MNDCMs),with regeneration potential,could persist in adult mammalian heart.However,the heterogeneity of MNDCMs and changes during development remains to be illu...A small proportion of mononuclear diploid cardiomyocytes(MNDCMs),with regeneration potential,could persist in adult mammalian heart.However,the heterogeneity of MNDCMs and changes during development remains to be illuminated.To this end,12645 cardiac cells were generated from embryonic day 17.5 and postnatal days 2 and 8 mice by single-cell RNA sequencing.Three cardiac developmental paths were identified:two switching to cardiomyocytes(CM)maturation with close CM–fibroblast(FB)communications and one maintaining MNDCM status with least CM–FB communications.Proliferative MNDCMs having interactions with macrophages and non-proliferative MNDCMs(non-pMNDCMs)with minimal cell–cell communications were identified in the third path.The non-pMNDCMs possessed distinct properties:the lowest mitochondrial metabolisms,the highest glycolysis,and high expression of Myl4 and Tnni1.Single-nucleus RNA sequencing and immunohistochemical staining further proved that the Myl4^(+)Tnni1+MNDCMs persisted in embryonic and adult hearts.These MNDCMs were mapped to the heart by integrating the spatial and single-cell transcriptomic data.In conclusion,a novel non-pMNDCM subpopulation with minimal cell–cell communications was unveiled,highlighting the importance of microenvironment contribution to CM fate during maturation.These findings could improve the understanding of MNDCM heterogeneity and cardiac development,thus providing new clues for approaches to effective cardiac regeneration.展开更多
As the continuous development of the industrial revolution,nanomaterials with excellent characteristics have been widely applied in various fields,greatly increasing the probability of human exposure to nanomaterials ...As the continuous development of the industrial revolution,nanomaterials with excellent characteristics have been widely applied in various fields,greatly increasing the probability of human exposure to nanomaterials and the concerns about the potential nanotoxicity.Existing studies have shown that the toxicity of nanomaterials may be closely related to oxidative stress,inflammatory response,phagocytosis dysfunction,DNA damage,etc.Based on our focus,nanomaterials may cross the human barrier through various channels and disrupt various cell-cell junctions,while the integrity of cellular barrier is a necessary for the normal physiological function of various organs.However,until now,there is still a lack of systematic discussion in this field.This review illustrates the importance of cell-cell junctions in maintaining various organ functions and highlights the mechanism of various nanomaterials disrupt cell-cell junctions,as well as the possible damage to various organs,such as brain,eye,lung,breast,intestine,placenta,testis,heart,liver,kidney,skin,etc.Awareness of the potential negative effects of nanomaterials will help scientists deeply understand the limitations of nanotechnology,inspiring them to develop safer and more efficient nanomaterials for future personalized nanomedicine.展开更多
Discovering novel drugs for cancer immunotherapy requires a robust in vitro drug screening platform that allows for straightforward probing of cell-ceil communications. Here, we combined surface-enhanced Raman scatter...Discovering novel drugs for cancer immunotherapy requires a robust in vitro drug screening platform that allows for straightforward probing of cell-ceil communications. Here, we combined surface-enhanced Raman scattering （SERS） nanoprobes with microfluidic networks to monitor in situ the cancer-immune system intercellular communications. The microfluidic platform links up immune cells with cancer cells, where the cancer-cell secretions act as signaling mediators. First, gold@silver core--shell nanorods were employed to fabricate SERS immunoprobes for analysis of the signaling molecules. Multiple cancer secretions in a tumor microenvironment were quantitatively analyzed by a SERS-assisted three-dimensional （3D） barcode immunoassay with high sensitivity （1 ng/mL）. Second, in an on-chip cell proliferation assay, multiple immunosuppressive proteins secreted by cancer cells were found to inhibit activation of immune cells, indicating that the platform simulates the physiological process of cancer-immune system communications. Furthermore, potential drug candidates were tested on this platform. A quantitative SERS immunoassay was performed to evaluate drug efficacy at regulating the secretion behavior of cancer cells and the activity of immune cells. This assay showed the suitability of this platform for in vitro drug screening. It is expected that the fully integrated and highly automated SERS-microfluidic platform will become a powerful analytical tool for probing intercellular communications and should accelerate the discovery and clinical validation of novel druKs.展开更多
Micro fluidic chip has been applied in various biological fields owing to its low-consumption of reagents, high throughput, fuidic controllability and integrity. The well-designed microscale intermediary is also ideal...Micro fluidic chip has been applied in various biological fields owing to its low-consumption of reagents, high throughput, fuidic controllability and integrity. The well-designed microscale intermediary is also ideal for the study of cell biology. Particularly, microfluidic chip is helpful for better understanding cell-cell interactions. A general survey of recent publications would help to generalize the designs of the co-culture chips with different features. With ingenious and combinational utilization, the chips facilitate the implementation of some special coculture models that are highly concerned in a different spatial and temporal way.展开更多
The evolution of seeds is a major reason why flowering plants are a dominant life form on Earth.The developing seed is composed of two fertilization products,the embryo and endosperm,which are surrounded by a maternal...The evolution of seeds is a major reason why flowering plants are a dominant life form on Earth.The developing seed is composed of two fertilization products,the embryo and endosperm,which are surrounded by a maternally derived seed coat.Accumulating evidence indicates that efficient communication among all three seed components is required to ensure coordinated seed development.Cell communication within plant seeds has drawn much attention in recent years.In this study,we review current knowledge of cross-talk among the endosperm,embryo,and seed coat during seed development,and highlight recent advances in this field.展开更多
The understanding of the macroscopic phenomenological models of the population growth at a microscopic level is important to predict the population behaviors emerged from the interactions between the individuals. In t...The understanding of the macroscopic phenomenological models of the population growth at a microscopic level is important to predict the population behaviors emerged from the interactions between the individuals. In this work, we consider the influence of the population growth rate R on the cell-cell interaction in a tumor system and show that, in most cases especially small proliferative probabilities, the regulative role of the interaction will be strengthened with the decline of the intrinsic proliferative probabilities. For the high replication rates of an individual and the cooperative interactions, the proliferative probability almost has no effect. We compute the dependences of R on the interactions between the cells under the approximation of the nearest neighbor in the rim of an avascular tumor. Our results are helpful to qualitatively understand the influence of the interactions between the individuals on the growth rate in population systems.展开更多
Cell-cell communication is the basis of physiological processes and cell signals.The disease occurs when the cells do not adequately communicate and the messages are blocked.With ligand-receptor interaction databases ...Cell-cell communication is the basis of physiological processes and cell signals.The disease occurs when the cells do not adequately communicate and the messages are blocked.With ligand-receptor interaction databases and single-cell RNA sequencing(scRNA-seq)databases,we can detect intercellular signaling and reconstruct the cell-cell communications among different cell types.This review summarized the computational approaches for analyzing the cell-cell communication based on scRNA-seq data and discussed its applications in carcinogenesis and COVID-19.We believe that this review will accelerate the scRNA-seq data deciphering and facilitate the cell-cell communication studies for complex physiological processes,such as carcinogenesis and SARS-CoV-2 infection.展开更多
基金supported by the National Natural Science Foundation of China(82271645)National Key Research and Development Program of China(2021YFC2700200 to F.S.)。
文摘Meiosis is a highly complex process significantly influenced by transcriptional regulation.However,studies on the mechanisms that govern transcriptomic changes during meiosis,especially in prophase I,are limited.Here,we performed single-cell ATAC-seq of human testis tissues and observed reprogramming during the transition from zygotene to pachytene spermatocytes.This event,conserved in mice,involved the deactivation of genes associated with meiosis after reprogramming and the activation of those related to spermatogenesis before their functional onset.Furthermore,we identified 282 transcriptional regulators(TRs)that underwent activation or deactivation subsequent to this process.Evidence suggested that physical contact signals from Sertoli cells may regulate these TRs in spermatocytes,while secreted ENHO signals may alter metabolic patterns in these cells.Our results further indicated that defective transcriptional reprogramming may be associated with non-obstructive azoospermia(NOA).This study revealed the importance of both physical contact and secreted signals between Sertoli cells and germ cells in meiotic progression.
基金Supported by Scientific and Technological Project of Henan Province,No.212102210140.
文摘BACKGROUND Liver cancer is one of the deadliest malignant tumors worldwide.Immunotherapy has provided hope to patients with advanced liver cancer,but only a small fraction of patients benefit from this treatment due to individual differences.Identifying immune-related gene signatures in liver cancer patients not only aids physicians in cancer diagnosis but also offers personalized treatment strategies,thereby improving patient survival rates.Although several methods have been developed to predict the prognosis and immunotherapeutic efficacy in patients with liver cancer,the impact of cell-cell interactions in the tumor microenvir-onment has not been adequately considered.AIM To identify immune-related gene signals for predicting liver cancer prognosis and immunotherapy efficacy.METHODS Cell grouping and cell-cell communication analysis were performed on single-cell RNA-sequencing data to identify highly active cell groups in immune-related pathways.Highly active immune cells were identified by intersecting the highly active cell groups with B cells and T cells.The significantly differentially expressed genes between highly active immune cells and other cells were subsequently selected as features,and a least absolute shrinkage and selection operator(LASSO)regression model was constructed to screen for diagnostic-related features.Fourteen genes that were selected more than 5 times in 10 LASSO regression experiments were included in a multivariable Cox regression model.Finally,3 genes(stathmin 1,cofilin 1,and C-C chemokine ligand 5)significantly associated with survival were identified and used to construct an immune-related gene signature.RESULTS The immune-related gene signature composed of stathmin 1,cofilin 1,and C-C chemokine ligand 5 was identified through cell-cell communication.The effectiveness of the identified gene signature was validated based on experi-mental results of predictive immunotherapy response,tumor mutation burden analysis,immune cell infiltration analysis,survival analysis,and expression analysis.CONCLUSION The findings suggest that the identified gene signature may contribute to a deeper understanding of the activity patterns of immune cells in the liver tumor microenvironment,providing insights for personalized treatment strategies.
基金supported by the National Natural Science Foundation of China,Nos.32271042 and 31871062(to XL)。
文摘Dorsal root ganglion neurons transmit peripheral somatic information to the central nervous system,and dorsal root ganglion neuron excitability affects pain perception.Dorsal root ganglion stimulation is a new approach for managing pain sensation.Knowledge of the cell-cell communication among dorsal root ganglion cells may help in the development of new pain and itch management strategies.Here,we used the single-cell RNA-sequencing(scRNA-seq)database to investigate intercellular communication networks among dorsal root ganglion cells.We collected scRNA-seq data from six samples from three studies,yielding data on a total of 17,766 cells.Based on genetic profiles,we identified satellite glial cells,Schwann cells,neurons,vascular endothelial cells,immune cells,fibroblasts,and vascular smooth muscle cells.Further analysis revealed that eight types of dorsal root ganglion neurons mediated proprioceptive,itch,touch,mechanical,heat,and cold sensations.Moreover,we predicted several distinct forms of intercellular communication among dorsal root ganglion cells,including cell-cell contact,secreted signals,extracellular matrix,and neurotransmitter-mediated signals.The data mining predicted that Mrgpra3-positive neurons robustly express the genes encoding the adenosine Adora2b(A2B)receptor and glial cell line-derived neurotrophic factor family receptor alpha 1(GFRα-1).Our immunohistochemistry results confirmed the coexpression of the A2B receptor and GFRα-1.Intrathecal injection of the A2B receptor antagonist PSB-603 effectively prevented histamine-induced scratching behaviour in a dose-dependent manner.Our results demonstrate the involvement of the A2B receptor in the modulation of itch sensation.Furthermore,our findings provide insight into dorsal root ganglion cell-cell communication patterns and mechanisms.Our results should contribute to the development of new strategies for the regulation of dorsal root ganglion excitability.
基金Supported by Past and present funding in the senior author’s laboratory as follows--Health Research Board of Ireland(HRA--POR-2014-545HRA/2009/49+6 种基金RP/2006/95,to Hopkins AM)Science Foundation Ireland(13/IA/19942008/RFP/NSC14272008/RFP/NSC1427 TIDA Feasibility 10,to Hopkins AM)Cancer Research Ireland,Breast Cancer IrelandBrazil Science Without Borders(CAPES-13306-13-8)the Beaumont Hospital Cancer Research and Development Trust
文摘Cell-cell and cell-matrix signaling and communication between adhesion sites involve mechanisms which are required for cellular functions during normal development and homeostasis; however these cellular functions and mechanisms are often deregulated in cancer. Aberrant signaling at cell-cell and cell-matrix adhesion sites often involves downstream mediators including Rho GTPases and tyrosine kinases. This review discusses these molecules as putative mediators of cellular crosstalk between cell-cell and cell-matrix adhesion sites, in addition to their attractiveness as therapeutic targets in cancer. Interestingly, inter-junctional crosstalk mechanisms are frequently typified by the way in which bacterial and viral pathogens opportunistically infect or intoxicate mammalian cells. This review therefore also discusses the concept of learning from pathogen-host interaction studies to better understand coordinated communication between cell-cell and cell-matrix adhesion sites, in addition to highlighting the potential therapeutic usefulness of exploiting pathogens or their products to tap into inter-junctional crosstalk. Taken together, we feel that increased knowledge around mechanisms of cell-cell and cell-matrix adhesion site crosstalk and consequently a greater understanding of their therapeutic targeting offers a unique opportunity to contribute to the emerging molecular revolution in cancer biology.
基金supported financially by Natural Science Foundation of China ( 11532003,11872129, 31670950)Natural Science Foundation of Jiangsu Province ( BK20181416)CZSTB Grant ( CZ20180017) from Changzhou City,Jiangsu Province
文摘Mechanobiology has been a highly recognized field in studying the importance of physical forces in physiologies at the molecular,cellular,tissue,organ and body-levels.Beside the intensive work focusing on the fine local biomechanical forces,the long-range force which can propagate through a relatively distant scale(in hundreds of micrometers and beyond)has been an intriguing topic with increasing attentions in recent years.The collective functions at cell population level often rely on cell-cell communications with or without direct contacts.Recent progresses including our own work indicate that the long-range biomechanical force propagating across scales far beyond single cell size may reserve the capability to trigger coordinative biological responses within cell population.Whether and how cells communicate mechanically in a distant manner remains largely to be explored.In respiratory system,the mechanical property of airway smooth muscle(ASM)is associated with asthma attack with prolonged contraction during airway hyper-responsiveness.In this work,we found that ASM cells rapidly self-assembled into a well-constructed network on 3D matrigel containing type I collagen(COL I),which required the collective functions and coordination of thousands of cells completed within 12-16 hours.Cells were assembled with aligned actin stress fibers and elongated nuclei.The assembling process relied on the long-range mechanical forces across the matrix to direct cell-cell distant interactions.We further found that single ASM cells could rapidly initiate multiple buds precisely pointing to neighboring cells in distance,which relied on cell traction force and force strain on the matrix.Beads tracking assay demonstrated the long-range transmission of cellular traction force to distant locations,and modeling of maximum strain distribution on matrix by finite element method predicted the consistency with cell directional protrusions and movements in experiments.Cells could sense each other in distance to move directionally on both non-fibrous matrigel and in much more efficient way when containing COL I.Cells recruited COL I from the hydrogel to build nearly identical COL I fibrous network to mechanically stabilize the cell network.Our results revealed that ASM cells can sense the traction strain transmitted through matrix to initiate distant communications and rapidly coordinate the network assembly at the population level through active cell-matrix interactions.As an interesting phenomenon,cells sound able to’make phone call’via the role of long-range mechanical force.In summary,this work demonstrated that long-range biomechanical force facilitates the collective functions of ASM cell population for network assembly.The cells reacted to traction strain on the matrix for distant communications,which resulted in directional budding and movement.Fibrous COL I had important roles in facilitating the efficiency of force transmission to induce the assembly and stabilizing the cell network.This work has helped advance the understanding of the feature andfunction of long-range biomechanical force at the cell population level.The observed high mechano-sensitivity of ASM cells might suggest a re-enforced feedback of enhanced contraction by excessive ASM under asthmatic condition.
基金National Natural Science Foundation of China,No.81872412,No.81602303,and No.31700736Hubei Province Natural Science Foundation of China,No.2016CFB180 and No.2017CFB786+3 种基金Health and Family Planning Commission of Hubei Province,No.WJ2016Y07 and No.WJ2016Y10Hubei Province Scientific and Technological Research Project,No.Q20171306Jingzhou Science and Technology Development Planning Project,No.JZKJ15063Guangzhou Key Medical Discipline Construction Project(CSZ),National Innovation and Entrepreneurship Training Program for College Students,No.202010489017。
文摘Tumor-initiating cells(TICs)or cancer stem cells are believed to be responsible for gastrointestinal tumor initiation,progression,metastasis,and drug resistance.It is hypothesized that gastrointestinal TICs(giTICs)might originate from cell-cell fusion.Here,we systemically evaluate the evidence that supports or opposes the hypothesis of giTIC generation from cell-cell fusion both in vitro and in vivo.We review giTICs that are capable of initiating tumors in vivo with 5000 or fewer in vivo fused cells.Under this restriction,there is currently little evidence demonstrating that giTICs originate from cell-cell fusion in vivo.However,there are many reports showing that tumor generation in vitro occurs with more than 5000 fused cells.In addition,the mechanisms of giTIC generation via cell-cell fusion are poorly understood,and thus,we propose its potential mechanisms of action.We suggest that future research should focus on giTIC origination from cell-cell fusion in vivo,isolation or enrichment of giTICs that have tumor-initiating capabilities with 5000 or less in vivo fused cells,and further clarification of the underlying mechanisms.Our review of the current advances in our understanding of giTIC origination from cell-cell fusion may have significant implications for the understanding of carcinogenesis and future cancer therapeutic strategies targeting giTICs.
基金supported by the National Natural Science Foundation of China[82001020 and 81771047]research funding from West China School/Hospital of Stomatology,Sichuan University[RCDWJS2021-13]+1 种基金China Postdoctoral Science Foundation[2019M663525]the Science and Technology Project of Sichuan Province[2021YFG0238].
文摘Mechanical stiffness is recognized as a key physical factor and directs cell function via a mechanotransduction process,from extracellular physical cues to intracellular signaling cascades that affect transcriptional activity.Cells continually receive mechanical signals from both the surrounding matrix and adjacent cells.However,how mechanical stiffness cue at cell-substrate interfaces coordinates cell-cell junctions in guiding mesenchymal stem cell behaviors is poorly understood.Here,polydimethylsiloxane substrates with different stiffnesses were used to study mechanosensation/transduction mechanisms in controlling odontogenic differentiation of dental papilla cells(DPCs).DPC phenotypes(morphology and differentiation)changed in response to the applied force derived from stiff substrates.Significantly,higher expression of paxillin on stiffer substrates promoted DPC dentinogenesis.Upon treatment with siRNA to knockdown paxillin,N-cadherin increased mainly in the cytomembrane at the area of cell-cell contacts,whereasβ-catenin decreased in the nuclei.The result of a double luciferase reporter assay showed that stiffness promotedβ-catenin binding to TCF,which could coactivate the target genes associated with odontogenic differentiation,as evidenced by bioinformatics analysis.Finally,we determined that the addition of aβ-catenin inhibitor suppressed DPC mineralization in all the stiffness groups.Thus,our results indicated that a mechanotransduction process from cell-substrate interactions to cell-cell adhesions was required for DPC odontogenic differentiation under the stimulation of substrate stiffness.This finding suggests that stem cell fate specification under the stimulus of stiffness at the substrates is based on crosstalk between substrate interactions and adherens junctions,which provides an essential mechanism for cell-based tissue engineering.
基金supported by the National Key Research and Development Program of China (No.2021YFA1101901)the Fundamental Research Funds for the Central Universities,HUST (No.2021GCRC073).
文摘A small proportion of mononuclear diploid cardiomyocytes(MNDCMs),with regeneration potential,could persist in adult mammalian heart.However,the heterogeneity of MNDCMs and changes during development remains to be illuminated.To this end,12645 cardiac cells were generated from embryonic day 17.5 and postnatal days 2 and 8 mice by single-cell RNA sequencing.Three cardiac developmental paths were identified:two switching to cardiomyocytes(CM)maturation with close CM–fibroblast(FB)communications and one maintaining MNDCM status with least CM–FB communications.Proliferative MNDCMs having interactions with macrophages and non-proliferative MNDCMs(non-pMNDCMs)with minimal cell–cell communications were identified in the third path.The non-pMNDCMs possessed distinct properties:the lowest mitochondrial metabolisms,the highest glycolysis,and high expression of Myl4 and Tnni1.Single-nucleus RNA sequencing and immunohistochemical staining further proved that the Myl4^(+)Tnni1+MNDCMs persisted in embryonic and adult hearts.These MNDCMs were mapped to the heart by integrating the spatial and single-cell transcriptomic data.In conclusion,a novel non-pMNDCM subpopulation with minimal cell–cell communications was unveiled,highlighting the importance of microenvironment contribution to CM fate during maturation.These findings could improve the understanding of MNDCM heterogeneity and cardiac development,thus providing new clues for approaches to effective cardiac regeneration.
基金the National Natural Science Foundation of China(Nos.22104073 and 22004048)the Natural Science Foundation of Shandong Province of China(Nos.ZR2021QB119,2022HWYQ-079,and ZR2020QB171)the Youth Innovation Science and Technology Program of Shandong Provincial Universities(No.2021KJ100).
文摘As the continuous development of the industrial revolution,nanomaterials with excellent characteristics have been widely applied in various fields,greatly increasing the probability of human exposure to nanomaterials and the concerns about the potential nanotoxicity.Existing studies have shown that the toxicity of nanomaterials may be closely related to oxidative stress,inflammatory response,phagocytosis dysfunction,DNA damage,etc.Based on our focus,nanomaterials may cross the human barrier through various channels and disrupt various cell-cell junctions,while the integrity of cellular barrier is a necessary for the normal physiological function of various organs.However,until now,there is still a lack of systematic discussion in this field.This review illustrates the importance of cell-cell junctions in maintaining various organ functions and highlights the mechanism of various nanomaterials disrupt cell-cell junctions,as well as the possible damage to various organs,such as brain,eye,lung,breast,intestine,placenta,testis,heart,liver,kidney,skin,etc.Awareness of the potential negative effects of nanomaterials will help scientists deeply understand the limitations of nanotechnology,inspiring them to develop safer and more efficient nanomaterials for future personalized nanomedicine.
文摘Discovering novel drugs for cancer immunotherapy requires a robust in vitro drug screening platform that allows for straightforward probing of cell-ceil communications. Here, we combined surface-enhanced Raman scattering （SERS） nanoprobes with microfluidic networks to monitor in situ the cancer-immune system intercellular communications. The microfluidic platform links up immune cells with cancer cells, where the cancer-cell secretions act as signaling mediators. First, gold@silver core--shell nanorods were employed to fabricate SERS immunoprobes for analysis of the signaling molecules. Multiple cancer secretions in a tumor microenvironment were quantitatively analyzed by a SERS-assisted three-dimensional （3D） barcode immunoassay with high sensitivity （1 ng/mL）. Second, in an on-chip cell proliferation assay, multiple immunosuppressive proteins secreted by cancer cells were found to inhibit activation of immune cells, indicating that the platform simulates the physiological process of cancer-immune system communications. Furthermore, potential drug candidates were tested on this platform. A quantitative SERS immunoassay was performed to evaluate drug efficacy at regulating the secretion behavior of cancer cells and the activity of immune cells. This assay showed the suitability of this platform for in vitro drug screening. It is expected that the fully integrated and highly automated SERS-microfluidic platform will become a powerful analytical tool for probing intercellular communications and should accelerate the discovery and clinical validation of novel druKs.
文摘Micro fluidic chip has been applied in various biological fields owing to its low-consumption of reagents, high throughput, fuidic controllability and integrity. The well-designed microscale intermediary is also ideal for the study of cell biology. Particularly, microfluidic chip is helpful for better understanding cell-cell interactions. A general survey of recent publications would help to generalize the designs of the co-culture chips with different features. With ingenious and combinational utilization, the chips facilitate the implementation of some special coculture models that are highly concerned in a different spatial and temporal way.
基金funded by the grants from National Natural Science Foundation of China(31630094,31800264)。
文摘The evolution of seeds is a major reason why flowering plants are a dominant life form on Earth.The developing seed is composed of two fertilization products,the embryo and endosperm,which are surrounded by a maternally derived seed coat.Accumulating evidence indicates that efficient communication among all three seed components is required to ensure coordinated seed development.Cell communication within plant seeds has drawn much attention in recent years.In this study,we review current knowledge of cross-talk among the endosperm,embryo,and seed coat during seed development,and highlight recent advances in this field.
基金Supported by the National Natural Science Foundation of China under Grant Nos.11675008 and 21434001
文摘The understanding of the macroscopic phenomenological models of the population growth at a microscopic level is important to predict the population behaviors emerged from the interactions between the individuals. In this work, we consider the influence of the population growth rate R on the cell-cell interaction in a tumor system and show that, in most cases especially small proliferative probabilities, the regulative role of the interaction will be strengthened with the decline of the intrinsic proliferative probabilities. For the high replication rates of an individual and the cooperative interactions, the proliferative probability almost has no effect. We compute the dependences of R on the interactions between the cells under the approximation of the nearest neighbor in the rim of an avascular tumor. Our results are helpful to qualitatively understand the influence of the interactions between the individuals on the growth rate in population systems.
基金The study is sponsored by Strategic Priority Research Program of Chinese Academy of Sciences(XDB38050200,XDB38060100,XDA26040304),CAS-TWAS President's Fellowship Program(to Md Wahiduzzaman)for international Ph.D.students.
文摘Cell-cell communication is the basis of physiological processes and cell signals.The disease occurs when the cells do not adequately communicate and the messages are blocked.With ligand-receptor interaction databases and single-cell RNA sequencing(scRNA-seq)databases,we can detect intercellular signaling and reconstruct the cell-cell communications among different cell types.This review summarized the computational approaches for analyzing the cell-cell communication based on scRNA-seq data and discussed its applications in carcinogenesis and COVID-19.We believe that this review will accelerate the scRNA-seq data deciphering and facilitate the cell-cell communication studies for complex physiological processes,such as carcinogenesis and SARS-CoV-2 infection.
