Biology subjects

Zhao, T.

Publications and source records attributed to Zhao, T..

At least 127 records · Page 7Linked to original sources

bioRxiv2021

Extend Mixed Models to Multi-layer Neural Networks for Genomic Prediction Including Intermediate Omics Data

With the growing amount and diversity of intermediate omics data complementary to genomics (e.g., DNA methylation, gene expression, and protein abundance), there is a need to develop methods to incorporate intermediate omics data into conventional genomic evaluation. The omics data helps decode the multiple layers of regulation from genotypes to phenotypes, thus forms a connected multi-layer network naturally. We developed a new method named NN-LMM to model the multiple layers of regulation from genotypes to intermediate omics features, then to phenotypes, by extending conventional linear mixed models ("LMM") to multi-layer artificial neural networks ("NN"). NN-LMM incorporates intermediate omics features by adding middle layers between genotypes and phenotypes. Linear mixed models (e.g., pedigree-based BLUP, GBLUP, Bayesian Alphabet, single-step GBLUP, or single-step Bayesian Alphabet) can be used to sample marker effects or genetic values on intermediate omics features, and activation functions in neural networks are used to capture the nonlinear relationships between intermediate omics features and phenotypes. NN-LMM had significantly better prediction performance than the recently proposed single-step approach for genomic prediction with intermediate omics data. Compared to the single-step approach, NN-LMM can handle various patterns of missing omics measures, and allows nonlinear relationships between intermediate omics features and phenotypes. NN-LMM has been implemented in an open-source package called "JWAS".

genetics↗

bioRxiv2021

New insights into colorectal cancer liver metastasis carcinogenesis and its effect with moxibustion

BackgroundChemotherapeutic drugs creates severe adverse reactions for colorectal cancer. Moxibustion confers clinical benefits for postoperative patients undergoing chemotherapy, it will fill the blank period of western medicine treatment and provide useful help for tumor patients to prevent recurrence and metastasis, but the physiological mechanisms behind the antitumor effects are unclear. This study was aimed to determine the effect and characterize the differential cytokines and gene expression profiles in intrasplenic transplanted GFP-HCT-116 cells-induced tumors model by Pre-Mox, Post-Mox and Pre-Post-Mox intervention. MethodsHuman CRC cells with GFP fluorescence were implanted via intrasplenic injection into Balb/c nude mice spleens. Moxibustion stimulation was applied to the BL18 and ST36 acupoints. The model control (MC) group were given no treatment. Pre-Mox mice were received moxibustion for 2 weeks before HCT-116 cell injection. Post-Mox mice received moxibustion for 3 weeks after CRC cell injection. Pre-Post-Mox mice received moxibustion for 5 weeks (2 weeks before and 3 weeks after CRC cell injection). Peripheral bloods were collected, pooled and assayed using a RayBio(R) mouse inflammation antibody array. Multi-Analyte Suspension Array was opted for verification. RNA isolated from liver paracancerous tissues from the control group and the experimental groups was subjected to RNA-seq, and then screened out significant differences for in-depth verification. RESULTSThe results showed that moxibustion stimulation increased the survival rate and decreased CRC liver metastasis. With the help of Multi-Analyte Suspension Array and RNA-seq, we screened significant differential expression of cytokines and RNA, then further verified them. The metastasis rate decreased significantly from 100% (10/10, MC group) to 50% (6/12, Pre-Mox group), to 46% (6/13, Post-Mox group), and further to 25% (3/12, Pre-Post-Mox group). Cytokine chips were used significant differences were found in MIP-3, MDC, IL-6, and IL-1a. Transcriptomic analysis suggested that the low-dose combination of Pre-Mox and Post-Mox modulated larger gene sets than the single treatment. We identified a small subset of genes, like APOA4, IGFBP5, IGFBP6, TIMP1, and MGP, as potential molecular targets involved in the preventive action of the combination of Pre-Mox and Post-Mox. ConclusionsTaken together, the current results provide the first evidence in support of the chemopreventive effect of a combination of Pre-Mox and Post-Mox in CRC. Moreover, the cytokines and transcriptional profile obtained in our study may provide a framework for identifying the mechanisms underlying the carcinogenesis process from colonic cancer to liver metastasis as well as the cancer inhibitory effects and potential molecular targets of Pre-Post-Mox.

cancer biology↗

bioRxiv2021

Detection of allele-specific expression in spatial transcriptomics with spASE

Allele-specific expression (ASE), or the preferential expression of one allele, can be observed in transcriptomics data from early development throughout the lifespan. However, the prevalence of spatial and cell type-specific ASE variation remains unclear. Spatial transcriptomics technologies permit the study of spatial ASE patterns genome-wide at near-single-cell resolution. However, the data are highly sparse, and confounding between cell type and spatial location present further statistical challenges. Here, we introduce spASE (https://github.com/lulizou/spase), a computational framework for detecting spatial patterns in ASE within and across cell types from spatial transcriptomics data. To tackle the challenge presented by the low signal to noise ratio due to the sparsity of the data, we implement a spatial smoothing approach that greatly improves statistical power. We generated Slide-seqV2 data from the mouse hippocampus and detected ASE in X-chromosome genes, both within and across cell type, validating our ability to recover known ASE patterns. We demonstrate that our method can also identify cell type-specific effects, which we find can explain the majority of the spatial signal for autosomal genes. The findings facilitated by our method provide new insight into the uncharacterized landscape of spatial and cell type-specific ASE in the mouse hippocampus.

genomics↗

bioRxiv2021

Mapping Consistent, Reproducible, and Transcriptionally Relevant Connectome Hubs of the Human Brain

Human brain connectomes include sets of densely connected regions, known as connectome hubs, which play a vital role in understanding global brain communication, cognitive processing, and brain disorders. However, the consistency and reproducibility of functional connectome hubs anatomical localization have not been established to date and the genetic signatures underlying robust connectome hubs remain unknown. Here, we conduct the first worldwide, harmonized meta-connectomic analysis by pooling resting-state functional MRI data of 5,212 healthy young adults across 61 independent cohorts. We identify highly consistent and reproducible functional connectome hubs in heteromodal and unimodal regions both across cohorts and across individuals. These connectome hubs show heterogeneous connectivity profiles and are critical for both intra- and inter-network communications. Using post-mortem gene expression data, we show that these connectome hubs have a spatiotemporally distinctive transcriptomic pattern dominated by genes involved in the neuropeptide signaling pathway, neurodevelopmental processes, and metabolic processes. These results highlight the robustness of macroscopic connectome hubs and their potential cellular and molecular underpinnings.

neuroscience↗

bioRxiv2021

A retinal circuit that vetoes optokinetic responses to fast visual motion

Optokinetic nystagmus (OKN) complements the vestibulo-ocular reflex (VOR) to stabilize the retinal image during head rotation. OKN is driven by the ON direction-selective ganglion cells (ON DSGCs), a rare class of retinal output neuron that encodes both the direction and speed of global retinal slip. The cells and synaptic circuits that give ON DSGCs their directional tuning are well known, but those dictating their slow-speed preference (and thus OKNs) remain enigmatic. Here, we probe this circuit through patch recordings, functional imaging, genetic manipulation, and serial electron microscopic reconstruction in mouse retina. We confirm earlier evidence that feedforward glycinergic inhibition is the main suppressor of ON DSGC responses to fast motion and reveal a surprising source for this inhibition [boxh] the VGluT3 amacrine cell, a retinal interneuron that releases both glycine and glutamate, exciting some neurons and inhibiting others. We find that VGluT3 cells respond robustly to fast global motion and that their output reaches most RGC types, as well as a diverse group of amacrine and bipolar cells. They enhance the response of ON-OFF DSGCs to fast motion, while suppressing it in ON DSGCs. Together, our results identify a novel role for VGluT3 cells, limiting the range of retinal slip speeds that drive image-stabilizing eye movements. More broadly, they suggest VGluT3 cells shape the response of many RGCs and amacrine cells to fast motion.

neuroscience↗

bioRxiv2021

Comprehensive identification of fetal cis-regulatory elements in the human genome by single-cell multi-omics analysis

The regulatory programs driving early organogenesis in human is complex and still poorly understood. We performed parallel profiling of gene expression and chromatin accessibility to 28 human fetal tissue samples representing 14 organs in the first trimester. Collectively, we have generated 415,793 single-cell profiles. By integration analysis of transcriptome and chromatin accessibility, we detected 225 distinct cell types and 848,475 candidate accessible cis-regulatory elements (aCREs). By linking regulatory elements to their putative target genes, we identified not only 108,699 enhancers, but also 23,392 silencers elements. We uncovered thousands of genes regulated by both enhancers and silencers in an organ or cell-type-specific manner. Furthermore, our unique approach revealed a substantial proportion of distal DNA elements are transcribed CREs (tCREs), which show both open chromatin signal and transcription initiation activity of non-coding transcript. The landscape of fetal cis-regulatory elements facilitates the interpretation of the genetic variant of complex disease and infer the cell type of origin for cancer. Overall, our data provide a comprehensive map of the fetal cis-regulatory elements at single-cell resolution and a valuable resource for future study of human development and disease.

developmental biology↗

bioRxiv2021

Distance-dependent inhibition of translation initiation by downstream out-of-frame AUGs reveals that ribosome scans in a Brownian ratchet process

While eukaryotic ribosomes are widely presumed to scan mRNA for the AUG codon to initiate translation in a strictly 5'-3' movement (strictly unidirectional scanning model), other evidence has suggested that the ribosome uses small-amplitude 5'-3' and 3'-5' oscillations with a net 5'-3' movement to recognize the AUG codon (Brownian ratchet scanning model). Here, we generated 13,437 yeast variants, each with an ATG triplet placed downstream (dATGs) of the annotated ATG (aATG) codon of green fluorescent protein. We found that out-of-frame dATGs could inhibit translation at the aATG, but with diminishing strength over increasing distance between aATG and dATG, undetectable beyond [~]17 nt. Computational simulations revealed that each triplet is scanned back and forth approximately [~]10 times until an AUG codon is recognized. Collectively, our findings uncover the basic process by which eukaryotic ribosomes scan for initiation codons, and how this process could shape eukaryotic genome evolution and influence cancer development.

molecular biology↗

bioRxiv2021

Identification of Significant Gene Expression Changes in Multiple Perturbation Experiments using Knockoffs

MotivationLarge-scale multiple perturbation experiments have the potential to reveal a more detailed understanding of the molecular pathways that respond to genetic and environmental changes. A key question in these studies is which gene expression changes are important for the response to the perturbation. ResultsWe present here a method based on the model-X knockoffs framework to identify significant gene expression changes in multiple perturbation experiments. This approach makes no assumptions on the functional form of the dependence between the responses and the perturbations and provides finite sample false discovery rate control for the set of important gene expression responses. In a large-scale multiple perturbation gene expression data set from the Library of Integrated Network-Based Cellular Signature (LINCS) NIH program, we identified important genes whose expression is modulated in response to perturbation with anthracycline, vorinostat, trichostatin-a, geldanamycin, and sirolimus. Furthermore, we compared the set of important genes that respond to these small molecules to identify co-responsive pathways. Availability and Implementationhttps://github.com/flahertylab/deepYknockoff Contactpflaherty@umass.edu and zhaott0416@gmail.com Supplementary informationSupplementary data are available at Bioinformatics online.

bioinformatics↗

bioRxiv2021

Senataxin and RNase H2 act redundantly to suppress genome instability during class switch recombination

Class switch recombination generates antibody distinct isotypes critical to a robust adaptive immune system and defects are associated with auto-immune disorders and lymphomagenesis. Transcription is required during class switch to recruit the cytidine deaminase AID--an essential step for the formation of DNA double-strand breaks--and strongly induces the formation of R loops within the immunoglobulin heavy chain locus. However, the impact of R loops on double-strand break formation and repair during class switch recombination remains unclear. Here we report that cells lacking two enzymes involved in R loop removal-- Senataxin and RNase H2--exhibit increased R loop formation and genome instability at the immunoglobulin heavy chain locus without impacting class switch recombination efficiency, transcriptional activity, or AID recruitment. Senataxin and RNase H2-deficient cells also exhibit increased insertion mutations at switch junctions, a hallmark of alternative end joining. Importantly, these phenotypes were not observed in cells lacking Senataxin or RNase H2B alone. We propose that Senataxin acts redundantly with RNase H2 to mediate timely R loop removal, promoting efficient repair while suppressing AID-dependent genome instability and insertional mutagenesis.

immunology↗

bioRxiv2021

Large-scale miRNA-Target Data Analysis to Discover miRNA Co-regulation Network of Abiotic Stress Tolerance in Soybeans

Although growing evidence shows that microRNA (miRNA) regulates plant growth and development, miRNA regulatory networks in plants are not well understood. Current experimental studies cannot characterize miRNA regulatory networks on a large scale. This information gap provides a good opportunity to employ computational methods for global analysis and to generate useful models and hypotheses. To address this opportunity, we collected miRNA-target interactions (MTIs) and used MTIs from Arabidopsis thaliana and Medicago truncatula to predict homologous MTIs in soybeans, resulting in 80,235 soybean MTIs in total. A multi-level iterative bi-clustering method was developed to identify 483 soybean miRNA-target regulatory modules (MTRMs). Furthermore, we collected soybean miRNA expression data and corresponding gene expression data in response to abiotic stresses. By clustering these data, 37 MTRMs related to abiotic stresses were identified including stress-specific MTRMs and shared MTRMs. These MTRMs have gene ontology (GO) enrichment in resistance response, iron transport, positive growth regulation, etc. Our study predicts soybean miRNA-target regulatory modules with high confidence under different stresses, constructs miRNA-GO regulatory networks for MTRMs under different stresses and provides miRNA targeting hypotheses for experimental study. The method can be applied to other biological processes and other plants to elucidate miRNA co-regulation mechanisms.

plant biology↗

bioRxiv2021

Development of Functional Connectome Gradients during Childhood and Adolescence

Connectome mapping studies have documented a principal primary-to-transmodal gradient in the adult brain network, capturing a functional spectrum which ranges from perception and action to abstract cognition. However, how this gradient pattern develops and whether its development is linked to cognitive growth, topological reorganization, and gene expression profiles remain largely unknown. Using longitudinal resting-state functional magnetic resonance imaging data from 305 children (ages 6-14), we describe substantial changes in the primary-to-transmodal gradient between childhood and adolescence, including emergence as the principal gradient, expansion of global topography, and focal tuning in primary and default-mode regions. These gradient changes are mediated by developmental changes in network integration and segregation, and are associated with abstract processing functions such as working memory and expression levels of calcium ion regulated exocytosis, synaptic transmission, and axon and synapse part related genes. Our findings have implications for understanding connectome maturation principles in normal development and developmental disorders. TeaserOur study reported the maturation of the core connectome gradient and its association with cognitions and genes expression.

neuroscience↗

bioRxiv2021

Bioimage postprocessing based on discrete wavelet transform and Lucy-Richardson deconvolution methods

Accompanied with the increasing requirements of probing micro/nanoscopic structures of biological samples, a variety of image processing algorithms have been developed for visualization or to facilitate data analysis. However, it remains challenging to enhance both the signal-to-noise ratio and image resolution using a single algorithm. In this investigation, we propose an approach utilizing discrete wavelet transform (DWT) in combination with Lucy-Richardson (LR) deconvolution (DWDC). Our results demonstrate that the signal-to-noise ratio and resolution of live cells microtubule network are considerably improved, allowing recognition of features as small as 120 nm. Notably, the approach is independent of imaging system and shows robustness in processing fibrous structures, e.g. the cytoskeleton networks.

biophysics↗

bioRxiv2021

Oxidative phosphorylation safeguards pluripotency via UDP-N-acetylglucosamine

The roles of mitochondrial respiration in pluripotency remain largely unknown. We show here that mouse ESC mitochondria possess superior respiration capacity compared to somatic cell mitochondria, and oxidative phosphorylation (OXPHOS) generates the majority of cellular ATP in ESCs. Inhibition of OXPHOS results in extensive pluripotency and metabolic gene expression reprogram, leading to disruption of self-renewal and pluripotency. Metabolomics profiling identifies UDP-N-acetylglucosamine (UDP-GlcNAc) as one of the most significantly decreased metabolites in response to OXPHOS inhibition. The loss of ESC identity induced by OXPHOS inhibition can be ameliorated by directly adding GlcNAc both in vitro and in vivo. This work demonstrates that mitochondrial respiration, but not glycolysis, produces the majority of ATP in ESCs, and uncovers a novel mechanism whereby mitochondrial respiration is coupled with the hexosamine biosynthesis pathway to generate UDP-GlcNAc for ESC identity maintenance. SIGNIFICANCEOxidative phosphorylation (OXPHOS) and glycolysis are the two major pathways for generating ATP in mammalian cells. It is widely assumed that somatic cells utilize OXPHOS, whereas embryonic stem cells (ESCs) utilize glycolysis with low mitochondrial respiration rates even under aerobic conditions. However, the relative contribution of OXPHOS and glycolysis to ATP generation in ESCs, and the role of mitochondrial respiration in regulating ESC identity, have remained unclear. In this study, Cao et al demonstrate that mouse ESC mitochondria have a significantly higher respiration capacity than somatic cell mitochondria. Oxidative phosphorylation produces the majority of cellular ATP in mESCs and is coupled with the hexosamine biosynthesis pathway to generate UDP-GlcNAc for pluripotency maintenance. These findings define the function and mechanism of OXPHOS in regulating pluripotency, and challenge the traditional concept that mESCs rely on glycolysis over OXPHOS for their major supply of energy. HIGHLIGHTSO_LIESC mitochondria have a significantly higher respiration capability than somatic cell mitochondria C_LIO_LIOXPHOS, but not glycolysis, produces the majority of cellular ATP in ESCs C_LIO_LIOXPHOS inhibition induces a decrease in O-GlcNAcylation and the expression of pluripotency genes in blastocysts that can be partially rescued by adding GlcNAc C_LIO_LIOXPHOS is coupled with the hexosamine biosynthesis pathway for UDP-GlcNAc biosynthesis to maintain ESC identity C_LI

cell biology↗

bioRxiv2021

Bark beetles locate fungal symbionts by detecting volatile fungal metabolites of host tree resin monoterpenes

Outbreaks of the Eurasian spruce bark beetle (Ips typographus) have decimated millions of hectares of conifer forests in Europe in recent years. The ability of these 3-6 mm long insects to kill mature trees over a short period has been ascribed to two main factors: (1) mass attacks on the host tree to overcome tree defenses and (2) the presence of fungal symbionts that support successful beetle development in the tree. While the role of pheromones in coordinating mass attacks has been well studied, the role of chemical communication in maintaining the fungal symbiosis is poorly understood. We previously demonstrated that I. typographus can recognize beneficial fungal symbionts of the genera Grosmannia, Endoconidiophora and Ophiostoma by their de novo synthesized volatile compounds. Here, we hypothesize that the fungal symbionts of the bark beetles might metabolize spruce resin monoterpenes of the beetles host tree, Norway spruce (Picea abies), and that the volatile products could be used as cues by beetles for locating breeding sites with beneficial symbionts. We show that Grosmannia penicillata and other fungal symbionts altered the profile of spruce bark volatiles by converting the major monoterpenes into an attractive blend of oxygenated derivatives. Bornyl acetate was metabolized to camphor, and - and {beta}-pinene to trans-4-thujanol and other oxygenated products. Other co-occurring non-beneficial fungi (Trichoderma sp.) also produce oxygenated monoterpenes, but in non-attractive ratios. Extensive electrophysiological measurements showed that the bark beetle possesses dedicated olfactory sensory neurons for oxygenated metabolites. Compounds such as camphor and trans-4-thujanol attracted beetles at specific doses in olfactory experiments, and the presence of symbiotic fungi enhanced attraction of females to pheromones. Finally, we show that colonization of fungal symbionts on spruce bark diet stimulated beetles to make tunnels into the diet. Collectively, our study suggests that the blends of oxygenated metabolites of conifer monoterpenes produced by fungal symbionts are used by bark beetles as attractive cues to find breeding or feeding sites containing their essential microbial symbionts. The oxygenated metabolites may aid beetles in assessing the presence of the fungus, the defense status of the host tree and the density of conspecifics at potential feeding and breeding sites.

ecology↗

bioRxiv2021

Acquisition of cancer stem cell properties during EMT requires cell division

Cancer cells acquire stem cell and mesenchymal properties during epithelial-to-mesenchymal transition (EMT), facilitating metastasis and chemoresistance [1-6]. In this study, we find that mammary epithelial cells quickly develop mesenchymal phenotype in response to EMT-inducing signals; however, acquiring stemness takes several days and always requires a preceding mesenchymal program. In addition, we observe that carcinoma cells, over a period of time, switch their cell division from symmetrical differentiated type to symmetrical self-renewal type. Importantly, epithelial cells can gain mesenchymal properties without undergoing cell division, but cell disivion is vital for these cells to gain stem cell properties during EMT. The EMT-induced stemness signature (SC-sig) is capable of predicting progression-free and overall-survival of breast cancer patients but not the EMT-induced mesenchymal signature (M-sig). Collectively, our findings demonstrate that the use of mesenchymal markers alone is insufficient to identify tumors with metastatic and chemoresistance potential and emphasize that the markers of EMT-induced stem cell program are central for clinical prediction. Most importantly, our data, for the first time, demonstrate that acquisition of stem cell properties during EMT depends on cell division but not the mesenchymal program.

cell biology↗

bioRxiv2021

Foot scales in the Early Cretaceous bird Gansus yumenensis from China

Most modern birds have scales covering the foot and feathers elsewhere. Discoveries of fossil feathers attached to the metatarsus in non-avian dinosaurs and basal birds suggests that the avian scales are secondarily derived from feathers. However, our knowledge of early avian scales and their taphonomy is still limited, due to the scarcity of fossil record. Here we employ multiple techniques to characterize the morphological and chemical details preserved and investigate how they are preserved in the skin of IVPP V15077, a referred specimen of the Early Cretaceous Gansus yumenensis. Results show that two types of scales, scutellate and interstitial scales, are preserved in IVPP V15077, which, in combination with previous discovery of scutate and reticulate scales in other Early Cretaceous birds, indicates that all four types of scales present in modern birds have appeared in the Early Cretaceous. SEM observations and Raman analysis suggest that the skin of Gansus yumenensis may be pigmented. Elemental mapping indicates that aluminosilicates and calcium phosphate are involved in the mineralization of the skin.

paleontology↗

bioRxiv2021

The REF6-dependent H3K27 demethylation establishes transcriptional competence to promote germination in Arabidopsis

Seed germination is a critical developmental switch from a dormant state to active growth, which involves extensive changes in metabolism, gene expression and cellular identity. However, our understanding of epigenetic and transcriptional reprogramming during this process is limited. The histone H3 lysine 27 trimethylation (H3K27me3) plays a key role in regulating gene repression and cell fate specification. Here, we profile H3K27me3 dynamics and dissect the function of H3K27 demethylation during germination. Our temporal genome-wide profiling of H3K27me3 and transcription reveal delayed H3K27me3 reprogramming compared with transcriptomic changes during germination, with H3K27me3 changes mainly occurring when the embryo is entering into vegetative development. REF6-mediated H3K27 demethylation promotes germination but does not significantly contribute to H3K27me3 dynamics during germination, but rather stably establishes an H3K27me3-depleted state permissive to transcription. By analyzing REF6 genomic binding, we show that it is absent from mature embryo chromatin and gradually establishes occupancy during the course of germination to counteract increased PRC2 activity. Our study provides key insights into the dynamics of gene expression and H3K27me3 during seed germination and suggests the function of H3K27me3 in facilitating cell fate switch. Furthermore, we reveal the importance of H3K27 demethylation-established transcriptional competence in germination and likely other developmental processes.

plant biology↗

bioRxiv2021

Phase separation on cell surface: a mechanism of basic fibroblast growth factor signal transduction with heparan sulphate

Liquid-liquid phase separation (LLPS) driven by weak, multivalent interactions among biomolecules is an important means of cellular compartmentation and plays a central role in cellular processes including stress resistance, RNA processing and other cellular activities. Coordination of the condensates and inner membrane was recently revealed, mediating intracellular processes like cell signalling and cargo trafficking. Intracellular LLPS has been observed extensively in vivo, whereas LLPS in extracellular compartments has not been reported under physiological conditions. Here we show, for the first time, that basic fibroblast growth factor (bFGF) undergoes LLPS on the cell surface by interacting with heparan sulphate proteoglycans (HSPG) and the phase transition is required for effective downstream signalling. The condensation is driven by multivalent interactions between bFGF and sulpho-groups on heparan sulphate (HS), and dimerization and oligomerization of bFGF promote the LLPS process. Compared with free bFGF, phase separated bFGF with HS showed higher thermo stability, providing a potential mechanism for the preservation of bFGF activity. Furthermore, we have found that downstream signalling is triggered by phase separation of a ternary complex formed by bFGF, HSPGs and FGFR on cell surface. Our results revealed a molecular mechanism that HS can serve as a platform to promote extracellular proteins like bFGF to condensate on outer membrane, consequently coordinating the signal transduction activities. This novel finding expands the horizons of phase separation in vivo, providing a new dimension on how HSPG may regulate extracellular protein behaviour and cell signalling.

biochemistry↗