Biology subjects

Zhu, X.

Publications and source records attributed to Zhu, X..

At least 199 records · Page 11Linked to original sources

bioRxiv2023

In situ cryoET reveals inhibitor-induced perturbations in Pf80S GTPase interactions

Malaria parasites rely heavily on rapid, high fidelity protein synthesis to infect and replicate in human erythrocytes, making translation an attractive target for new antimalarials. Here, we have determined in situ structures of Pf80S ribosomes in thirteen conformational and compositional states from cryoFIB-milled Plasmodium falciparum-infected human erythrocytes across the stages of asexual intraerythrocytic parasite replication. We observe eight active translation intermediates, enabling us to define the native malarial translation elongation cycle, which surprisingly features a bifurcation at the decoding stage of the cycle that has not previously been described. Examination of perturbations in the distribution of ribosomes among these states in the presence of a malaria-specific translation inhibitor suggests that the inhibitor impedes PfeEF2 and PfeEF1 interactions with the ribosome. We integrated our in situ cryoET data with proteomic and ultrastructural data to arrive at a deeper understanding of malarial translation, which will inform development of new therapies.

biophysics↗

bioRxiv2023

Elimination of subtelomeric repeat sequences exerts little effect on telomere functions in Saccharomyces cerevisiae

Telomeres, which are chromosomal end structures, play a crucial role in maintaining genome stability and integrity in eukaryotes. In the bakers yeast Saccharomyces cerevisiae, the X-and Y-elements are subtelomeric repetitive sequences found in all thirty-two and seventeen telomeres, respectively. While the Y-elements serve as a backup for telomere functions in cells lacking telomerase, the function of the X-elements remains unclear. This study utilized the S. cerevisiae strain SY12, which has three chromosomes and six telomeres, to investigate the role of X-elements (as well as Y-elements) in telomere maintenance. Deletion of Y-elements (SY12Y{Delta}), X-elements (SY12XY{Delta}+Y), or both X- and Y-elements (SY12XY{Delta}) did not impact the length of the terminal TG1-3 tracks or telomere silencing. However, inactivation of telomerase in SY12Y{Delta}, SY12XY{Delta}+Y, and SY12XY{Delta} cells resulted in cellular senescence and the generation of survivors. These survivors either maintained their telomeres through homologous recombination-dependent TG1-3 track elongation or underwent microhomology-mediated intra-chromosomal end-to-end joining. Our findings indicate the non-essential role of subtelomeric X-and Y-elements in telomere regulation in both telomerase-proficient and telomerase-null cells and suggest that these elements may represent remnants of S. cerevisiae genome evolution. Furthermore, strains with fewer or no subtelomeric elements exhibit more concise telomere structures and offer potential models for future studies in telomere biology.

genetics↗

bioRxiv2023

Enhancing visual perceptual learning using transcranial electrical stimulation: transcranial alternating current stimulation outperforms both transcranial direct current and random noise stimulation

Diverse strategies can be employed to enhance visual skills, including visual perceptual learning (VPL) and transcranial electrical stimulation (tES). Combining VPL and tES is a popular method that holds promise for significant improvements in visual acuity within a short time frame. However, there is still a lack of comprehensive evaluation regarding the effects of combining different types of tES and VPL on enhancing visual function, especially with a larger sample size. In the present study, we recruited four groups of subjects (26 subjects each) to learn an orientation discrimination task with five daily training sessions. During training, subjects occipital region was stimulated by one type of tES (anodal transcranial direct current stimulation (tDCS), alternating current stimulation (tACS) at 10 Hz, high-frequency random noise stimulation (tRNS), and sham tACS) while performing the training task. We found that compared with the sham stimulation, both the high-frequency tRNS and the 10 Hz tACS facilitated VPL efficiently in terms of learning rate and performance improvement, while there was little modulatory effect in the anodal tDCS condition. Remarkably, the 10 Hz tACS condition exhibited superior modulatory effects to the tRNS condition, demonstrating the strongest modulation among the most commonly used tES types for further enhancing vision when combined with VPL. Our results suggest that alpha oscillations play a vital role in VPL. Our study provides a practical guide for vision rehabilitation.

neuroscience↗

bioRxiv2023

Dual-specificity protein phosphatase 6 (DUSP6) overexpression reduces amyloid load and improves memory deficits in male 5xFAD mice

BackgroundDual specificity protein phosphatase 6 (DUSP6) was recently identified as a key hub gene in a causal network that regulates late-onset Alzheimers disease. Importantly, decreased DUSP6 levels are correlated with an increased clinical dementia rating in human subjects, and DUSP6 levels are additionally decreased in the 5xFAD amyloidopathy mouse model. MethodsAAV5-DUSP6 or AAV5-GFP (control) were stereotactically injected into the dorsal hippocampus (dHc) of female and male 5xFAD or wild type mice to overexpress DUSP6 or GFP. Spatial learning memory of these mice was assessed in the Barnes maze, after which hippocampal tissues were isolated for downstream analysis. ResultsBarnes maze testing indicated that DUSP6 overexpression in the dHc of 5xFAD mice improved memory deficits and was associated with reduced amyloid plaque load, A{beta}1-40 and A{beta}1-42 levels, and amyloid precursor protein processing enzyme BACE1, in male but not in female mice. Microglial activation and microgliosis, which are increased in 5xFAD mice, were significantly reduced by dHc DUSP6 overexpression in both males and females. Transcriptomic profiling of female 5xFAD hippocampus revealed upregulated expression of genes involved in inflammatory and extracellular signal-regulated kinase (ERK) pathways, while dHc DUSP6 overexpression in female 5xFAD mice downregulated a subset of genes in these pathways. A limited number of differentially expressed genes (DEGs) (FDR<0.05) were identified in male mice; gene ontology analysis of DEGs (p<0.05) identified a greater number of synaptic pathways that were regulated by DUSP6 overexpression in male compared to female 5xFAD. Notably, the msh homeobox 3 gene, Msx3, previously shown to regulate microglial M1/M2 polarization and reduce neuroinflammation, was one of the most robustly upregulated genes in female and male wild type and 5xFAD mice overexpressing DUSP6. ConclusionsIn summary, our data indicate that DUSP6 overexpression in dHc reduced amyloid deposition and memory deficits in male but not female 5xFAD mice, whereas reduced neuroinflammation and microglial activation were observed in both males and females. The sex-dependent regulation of synaptic pathways by DUSP6 overexpression, however, correlated with the improvement of spatial memory deficits in male but not female 5xFAD.

neuroscience↗

bioRxiv2023

Microglial cannabinoid receptor type1 mediates social memory deficits produced by adolescent THC exposure and 16p11.2 duplication

Adolescent cannabis use increases the risk for cognitive impairments and psychiatric disorders. Cannabinoid receptor type 1 (Cnr1) is expressed not only in neurons and astrocytes, but also in microglia, which shape synaptic connections during adolescence. Nonetheless, until now, the role of microglia in mediating the adverse cognitive effects of delta-9-tetrahydrocannabinol (THC), the principal psychoactive constituent of cannabis, has been unexplored. Here, we report that adolescent THC exposure produces microglial apoptosis in the medial prefrontal cortex (mPFC), which was exacerbated in the mouse model of 16p11.2 duplication, a representative copy number variation (CNV) risk factor for psychiatric disorders. These effects are mediated by microglial Cnr1, leading to reduction in the excitability of mPFC pyramidal-tract neurons and deficits in social memory in adulthood. Our findings highlight the importance of microglial Cnr1 to produce the adverse effect of cannabis exposure in genetically vulnerable individuals.

neuroscience↗

bioRxiv2023

Massively Concurrent Sub-Cellular Traction Force Videography enabled by Single-Pixel Optical Tracers (SPOTs)

We report a large field-of-view and high-speed videography platform for measuring the sub-cellular traction forces of more than 10,000 biological cells over 13mm2 at 83 frames per second. Our Single-Pixel Optical Tracers (SPOT) tool uses 2-dimensional diffraction gratings embedded into a soft substrate to convert cells mechanical traction stress into optical colors detectable by a video camera. The platform measures the sub-cellular traction forces of diverse cell types, including tightly connected tissue sheets and near isolated cells. We used this platform to explore the mechanical wave propagation in a tightly connected sheet of Neonatal Rat Ventricular Myocytes (NRVMs) and discovered that the activation time of some tissue regions are heterogeneous from the overall spiral wave behavior of the cardiac wave. One-Sentence SummaryAn optical platform for fast, concurrent measurements of cell mechanics at 83 frames per second, over a large area of 13mm2.

bioengineering↗

bioRxiv2023

Host-microbiota interactions contributing to the heterogeneous tumor microenvironment in colorectal cancer

BackgroundColorectal cancer (CRC) is a highly heterogeneous cancer with four consensus molecular subtypes (CMSs) characterized by distinct tumor microenvironment (TME). We aimed to depict the characteristics of host-microbiota interactions and their contributions to TME in each CMS. MethodsHost transcriptome and intratumoral microbiome profiles of 594 CRC samples were derived from RNA-Seq data from TCGA. Differential host genes and microbes among CMSs were identified. Immune microenvironments were assessed by CIBERSORTx and ESTIMATE and microbial co-abundance analyses were performed by FastSpar. Host-microbiota associations were evaluated by LASSO penalized regression in each CMS. ResultsAlong with distinct host gene signatures, including ferroptosis-related genes and immune microenvironments, 293, 153, 66 and 109 intratumoral differential microbial genera were identified within each of the four CMSs, respectively. Furthermore, the host-microbiota interactions contributed to distinct TME in each CMS, represented by 829, 1,270, 634 and 1,882 robust gene-microbe associations, respectively. The TME in CMS1 was featured with inflammation-related HSF1 activation and interactions between genes of endothelin pathway and Flammeovirga. Integrins-related genes positively correlated with Sutterella in CMS2 while CMS3 displayed microbial associations with biosynthetic and metabolic pathways. Genes in collagens biosynthesis positively correlated with Sutterella, contributing to homeostasis disturbance in CMS4. Besides, ferroptosis dysregulation was more remarkable in immune-high subtypes, which might partly result from the colonization of tissue microbes. ConclusionsWe systematically profiled the landscapes of TME, of each CMS in CRC, encompassing host genes, intratumoral microbiome and their interactions, which could illuminate novel mechanisms for the heterogeneity in CRC and potential therapeutic targets.

microbiology↗

bioRxiv2023

A microfluidic strategy to capture antigen-specific high affinity B cells

Assessing B cell affinity to pathogen-specific antigens prior to or following exposure could facilitate the assessment of immune status. Current standard tools to assess antigen-specific B cell responses focus on equilibrium binding of the secreted antibody in serum. These methods are costly, time-consuming, and assess antibody affinity under zero-force. Recent findings indicate that force may influence BCR-antigen binding interactions and thus immune status. Here, we designed a simple laminar flow microfluidic chamber in which the antigen (hemagglutinin of influenza A) is bound to the chamber surface to assess antigen-specific BCR binding affinity of five hemagglutinin-specific hybridomas under 65- to 650-pN force range. Our results demonstrate that both increasing shear force and bound lifetime can be used to enrich antigen-specific high affinity B cells. The affinity of the membrane-bound BCR in the flow chamber correlates well with the affinity of the matched antibodies measured in solution. These findings demonstrate that a microfluidic strategy can rapidly assess BCR-antigen binding properties and identify antigen-specific high affinity B cells. This strategy has the potential to both assess functional immune status from peripheral B cells and be a cost-effective way of identifying individual B cells as antibody sources for a range of clinical applications.

bioengineering↗

bioRxiv2023

Salmonella enterica serovar Typhimurium ST313 sublineage 2.2 has emerged in Malawi with a characteristic gene expression signature and a fitness advantage

Invasive non-typhoidal Salmonella (iNTS) disease is a serious bloodstream infection that targets immune-compromised individuals, and causes significant mortality in sub-Saharan Africa. Salmonella enterica serovar Typhimurium ST313 causes the majority of iNTS in Malawi, and we performed an intensive comparative genomic analysis of 608 isolates obtained from fever surveillance at the Queen Elizabeth Hospital, Blantyre between 1996 and 2018. We discovered that following the upsurge of the well-characterised S. Typhimurium ST313 lineage 2 from 1999 onwards, two new multidrug-resistant sublineages designated 2.2 and 2.3, emerged in Malawi in 2006 and 2008, respectively. The majority of S. Typhimurium isolates from human bloodstream infections in Malawi now belong to sublineage 2.2 or 2.3. To identify factors that characterised the emergence of the prevalent ST313 sublineage 2.2, we performed genomic and functional analysis of two representative strains, D23580 (lineage 2) and D37712 (sublineage 2.2). Comparative genomic analysis showed that the chromosome of ST313 lineage 2 and sublineage 2.2 were broadly similar, only differing by 29 SNPs and small indels and a 3kb deletion in the Gifsy-2 prophage region that spanned the sseI pseudogene. Lineage 2 and sublineage 2.2 have unique plasmid profiles that were verified by long read sequencing. The transcriptome was initially explored in 15 infection-relevant conditions and within macrophages. Differential gene expression was subsequently investigated in depth in the four most important in vitro growth conditions. We identified up-regulation of SPI2 genes in non-inducing conditions, and down-regulation of flagellar genes in D37712, compared to D23580. Following phenotypic confirmation of transcriptional differences, we discovered that sublineage 2.2 had increased fitness compared with lineage 2 during mixed-growth in minimal media. We speculate that this competitive advantage is contributing to the continuing presence of sublineage 2.2 in Malawi.

bioinformatics↗

bioRxiv2023

Sustained hippocampal theta-oscillations reflect experience-dependent learning in bidirectional temporal-order memory retrieval

Navigating within our neighborhood, learning a set of concepts, or memorizing a story, requires remembering the relationship between individual items that are presented sequentially. Theta activity in the mammalian hippocampus has been related to the encoding and recall of relational structures embedding episodic memories. However, how theta oscillations are involved in retrieving temporal order information in opposing directionality (forward vs backward) has not been characterized. Here, using intracranial recordings from 10 human epileptic patients of both genders with hippocampal electrodes, we tested the patients with a temporal order memory task in which they learned the spatial relationship among individual items arranged along a circular track and were tested on both forward-cued and backward-cued retrieval conditions. We found that sustained high-power oscillatory events in the hippocampal theta (2-8 Hz) band, as quantified by Pepisode rate, were higher for the backward conditions during the later stage but not in the earlier stage. The theta Pepisode results are consistent with the behavioral memory performance. In contrast, we observed a stronger effect of forward than backward retrieval for the gamma (30-70 Hz) Pepisode rate irrespective of stages. Our results revealed differential roles of theta vs. gamma oscillations in the retrieval of temporal order and how theta oscillations are specifically implicated in the learning process for efficient retrieval of temporal order memories under opposing directionality. Significance statementWhile the hippocampus is critical to link events into unitary episodes, the effect of repeated experiences, or learning, on these processes is not entirely clear. We discovered that hippocampal theta oscillation in humans is modulated by repeated experiences, which in turn increases the efficacy of backward-cued memory retrieval of temporal order. This study revealed an important physiological signature characterizing the role of experiences and learning in bidirectional temporal memory retrieval. Journal sectionBehavioral/Cognitive

neuroscience↗

bioRxiv2023

A framework for Frizzled-G protein coupling and implications to the Wnt-PCP signaling pathways

The ten Frizzled receptors (FZDs) are essential in Wnt signaling and play important roles in embryonic development and tumorigenesis. Among these, FZD6 is closely associated with lens development. Understanding FZD activation mechanism is key to unlock these emerging targets. Here we present the cryo-EM structures of FZD6 and FZD3 which are known to relay non-canonical Wnt-PCP (planar cell polarity) signaling pathways as well as FZD1 in their G protein-coupled (active) and G protein-free (inactive) states, respectively. Comparison of the three inactive/active pairs unveiled a shared activation framework among all ten FZDs. Mutagenesis along with imaging and functional analysis on the human lens epithelial tissues suggested potential crosstalk between G-protein binding and Wnt-PCP signaling pathways. Together, this study provides an integrated understanding of FZD structure and function, and lays the foundation for developing therapeutic modulators to activate or inhibit FZD signaling for a range of disorders including cancers and cataracts.

biochemistry↗

bioRxiv2023

The ChickenGTEx pilot analysis: a reference of regulatory variants across 28 chicken tissues

Chicken is a valuable model for understanding fundamental biology, vertebrate evolution and diseases, as well as a major source of nutrient-dense and lean-protein-enriched food globally. Although it is the first non-mammalian amniote genome to be sequenced, the chicken genome still lacks a systematic characterization of functional impacts of genetic variants. Here, through integrating 7,015 RNA-Seq and 2,869 whole-genome sequence data, the Chicken Genotype- Tissue Expression (ChickenGTEx) project presents the pilot reference of regulatory variants in 28 chicken tissue transcriptomes, including millions of regulatory effects on primary expression (including protein-coding genes, lncRNA and exon) and post-transcriptional modifications (alternative splicing and 3 untranslated region alternative polyadenylation). We explored the tissue-sharing and context-specificity of these regulatory variants, their underlying molecular mechanisms of action, and their utility in interpreting adaptation and genome-wide associations of 108 chicken complex traits. Finally, we illustrated shared and lineage-specific features of gene regulation between chickens and mammals, and demonstrated how the ChickenGTEx resource can further assist with translating genetic findings across species. One-Sentence SummaryThe ChickenGTEx provides a multi-tissue reference of regulatory variants for chicken genetics and genomics, functional genomics, precision breeding, veterinary medicine, vertebrate evolution and even human biomedicine.

genetics↗

bioRxiv2023

Genome-wide identification of silencers in human cells

Transcriptional regulation is a complex process that is controlled by a variety of factors, including enhancers and silencers. Silencers, also known as repressor elements, play a crucial role in the fine-tuning of gene expression by inhibiting or suppressing transcription in the human genome. Although significant progresses have been made, genome-wide silencer research is still in its early stages. Here, we used a genome-wide method called massively parallel reporter assays (MPRAs) to identify silencers in three human cell lines: K562, LNCap, and HEK293T. We identified 739,434, 643,484, and 491,952 silencer regions in these cell lines, respectively. We found that most of the silencers we identified had inhibitory activity and significantly enriched inhibitory motifs. These results confirm that silencers are ubiquitous in the human genome and play an important role in regulating gene expression. Therefore, our study provides a general strategy for genome-wide functional identification of silencer elements. This information could be used to better understand the mechanisms of gene regulation and to develop new therapeutic strategies for diseases that are caused by dysregulation of gene expression.

genomics↗

bioRxiv2023

Dissecting peri-implantation development using cultured human embryos and embryo-like assembloids

Studies of cultured embryos have provided insights into human peri-implantation development. However, detailed knowledge of peri-implantation lineage developments as well as underlying mechanisms remain obscure. Using 3D-cultured human embryos, herein we report a complete cell atlas of the early post-implantation lineages and decipher cellular composition and gene signatures of the epiblast and hypoblast derivatives. In addition, we develop an embryo-like assembloid (E-assembloid) by assembling naive hESCs and extraembryonic cells. Using human embryos and E-assembloids, we reveal that WNT, BMP and Nodal signaling synergistically, but functionally differently, orchestrate human peri-implantation lineage development. Specially, we dissect mechanisms underlying extraembryonic mesoderm and extraembryonic endoderm specifications. Finally, an improved E-assembloid is developed to recapitulate the epiblast and hypoblast developments and tissue architectures in the pre-gastrulation human embryo. Our findings provide insights of the human peri-implantation development, and the E-assembloid offers a useful model to disentangle cellular behaviors and signaling interactions that drive human embryogenesis.

developmental biology↗

bioRxiv2023

RETROFIT: REFERENCE-FREE DECONVOLUTION OF CELL-TYPE MIXTURES IN SPATIAL TRANSCRIPTOMICS

Spatial transcriptomics (ST) enables genome-wide measurement of gene expression in intact tissues, but typically captures mixtures of multiple cell types at each spatial location. Deconvolving these mixtures is essential for resolving cell-type-specific spatial organization and transcriptional programs. Existing approaches often rely on matched single-cell references or curated marker genes, which may be unavailable, incomplete, or difficult to integrate across platforms. We present RETROFIT, a Bayesian framework for reference-free deconvolution of spatial transcriptomics data that operates directly on sequencing measurements and incorporates external information only at a post hoc annotation stage when available. Across extensive simulations and multiple real datasets, RETROFIT demonstrates robust performance, outperforming existing reference-free methods and matching or exceeding reference-based approaches when references are imperfect. Notably, RETROFIT remains effective at near-single-cell resolution, as demonstrated on Visium HD data, recovering fine-grained spatial patterns without requiring single-cell references or marker genes. These results establish RETROFIT as a broadly applicable approach for reference-free spatial transcriptomics analysis across platforms and resolutions. RETROFIT is available at https://bioconductor.org/packages/retrofit/.

bioinformatics↗

bioRxiv2023

High-resolution structure of mouse radial spoke and its in-situ structure in ependymal cilia revealed by cryo-EM and cryo-ET

Radial spokes (RS) transmit mechanochemical signals between the central pair (CP) and axonemal dynein arms to coordinate ciliary motility. However, the high-resolution structure of mammalian RS remains missing. Here, we present the high-resolution cryo-EM structure of mouse RS head-neck complex in both monomer and dimer forms and reveal the intrinsic dynamics of the dimer. We also map the genetic mutations related to primary ciliary dyskinesia and asthenospermia on the head-neck complex. Moreover, we present the unprecedented cryo-ET and sub-tomogram averaging map of mouse ependymal cilia, whose beating creates unidirectional cerebrospinal fluid flow, and build the models for RS1-3, IDAs, and N-DRC. Strikingly, our cryo-ET map reveals the lack of IDA-b/c/e and the absence of tektin filaments within the A-tubule of doublet microtubules in ependymal cilia compared with mammalian respiratory cilia and sperm flagella. This tissue-specific feature may represent an evolutionary choice driven by the functional requirements on ependymal cilia. Our findings reveal the RS head-neck assembly mechanism, shed light on the coordinated rigid and elastic RS-CP interaction modes beneficial for the regulation of asymmetric ciliary beating, and also facilitate understandings on the etiology of ciliary dyskinesia-related ciliopathies.

biophysics↗

bioRxiv2023

HMGB1 acts as an agent of host defense at the gut mucosal barrier

Mucosal barriers provide the first line of defense between internal body surfaces and microbial threats from the outside world.1 In the colon, the barrier consists of two layers of mucus and a single layer of tightly interconnected epithelial cells supported by connective tissue and immune cells.2 Microbes colonize the loose, outer layer of colonic mucus, but are essentially excluded from the tight, epithelial-associated layer by host defenses.3 The amount and composition of the mucus is calibrated based on microbial signals and loss of even a single component of this mixture can destabilize microbial biogeography and increase the risk of disease.4-7 However, the specific components of mucus, their molecular microbial targets, and how they work to contain the gut microbiota are still largely unknown. Here we show that high mobility group box 1 (HMGB1), the prototypical damage-associated molecular pattern molecule (DAMP), acts as an agent of host mucosal defense in the colon. HMGB1 in colonic mucus targets an evolutionarily conserved amino acid sequence found in bacterial adhesins, including the well-characterized Enterobacteriaceae adhesin FimH. HMGB1 aggregates bacteria and blocks adhesin-carbohydrate interactions, inhibiting invasion through colonic mucus and adhesion to host cells. Exposure to HMGB1 also suppresses bacterial expression of FimH. In ulcerative colitis, HMGB1 mucosal defense is compromised, leading to tissue-adherent bacteria expressing FimH. Our results demonstrate a new, physiologic role for extracellular HMGB1 that refines its functions as a DAMP to include direct, virulence limiting effects on bacteria. The amino acid sequence targeted by HMGB1 appears to be broadly utilized by bacterial adhesins, critical for virulence, and differentially expressed by bacteria in commensal versus pathogenic states. These characteristics suggest that this amino acid sequence is a novel microbial virulence determinant and could be used to develop new approaches to diagnosis and treatment of bacterial disease that precisely identify and target virulent microbes.

microbiology↗

bioRxiv2023

TREM2 promotes glioma progression and angiogenesis mediated by microglia/brain macrophages

TREM2, a myeloid cell-specific signaling molecule, controls essential functions of microglia and impacts on the pathogenesis of Alzheimers disease and other neurodegenerative disorders. TREM2 is also highly expressed in tumor-associated macrophages and plays detrimental roles in an experimental mouse sarcoma model. Here we studied whether TREM2 influences glioma progression. We found a sex- dependent effect of TREM2: the glioma volume is significantly attenuated in TREM2- deficient male but not female mice injected with GL261-EGFP glioma cells. The accumulation of glioma-associated microglia/macrophages (GAMs) and vascularization is reduced in male TREM2-deficient mice. A transcriptomic analysis of glioma tissue revealed that TREM2 deficiency suppresses angiogenic genes and MHC clusters. In an organotypic slice model devoid of functional vascularization, the tumor size was not affected by TREM2-deficiency. In human resection samples from glioblastoma, TREM2 is upregulated in GAMs. Based on the TCGA and CGGA databases, the TREM2 expression levels are negatively correlated with survival. Thus, the TREM2-dependent crosstalk between GAMs and the vasculature formation promotes glioma growth. Graphic abstractTREM2-dependent crosstalk between glioma-associated microglia/macrophages and the vasculature formation promotes glioma growth in male glioma mouse model. Created with BioRender.com O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=137 SRC="FIGDIR/small/540621v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@65bec7org.highwire.dtl.DTLVardef@1d00961org.highwire.dtl.DTLVardef@117ee5eorg.highwire.dtl.DTLVardef@227994_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗