Biology subjects

Lin, T.

Publications and source records attributed to Lin, T..

At least 55 records · Page 3Linked to original sources

bioRxiv2023

Identification of a pharmaceutical biostasis inducer that slows metabolism in multiple vertebrates that do not hibernate

Drugs that induce reversible slowing of metabolic and physiological processes would have great value for organ preservation, especially for organs with high susceptibility to hypoxia-reperfusion injury, such as the heart. Using whole-organism screening of metabolism, mobility, and development in Xenopus, we identified an existing drug, SNC80, that rapidly and reversibly slows biochemical and metabolic activities while preserving cell and tissue viability. Although SNC80 was developed as a delta opioid receptor activator, we discovered that its ability to slow metabolism is independent of its opioid modulating activity as a novel SNC80 analog (WB3) with almost 1,000 times less delta opioid receptor binding activity is equally active. Metabolic suppression was also achieved using SNC80 in microfluidic human organs-on-chips, as well as in explanted whole porcine hearts and limbs, demonstrating the cross-species relevance of this approach and potential clinical relevance for surgical transplantation. Pharmacological induction of physiological slowing in combination with organ perfusion transport systems may offer a new therapeutic approach for tissue and organ preservation for transplantation, trauma management, and enhancing patient survival in remote and low-resource locations.

bioengineering↗

bioRxiv2023

Insulin determines the effects of TGF-beta on HNF4alpha transcription and epithelial-to-mesenchymal transition in hepatocytes

To date, epithelial-to-mesenchymal transition (EMT) has been observed in cultured hepatocytes, but not in vivo. TGF-{beta} is supposed to initiate EMT in hepatocytes by inhibiting HNF4 through the SMAD2/3 complex. We report that TGF-{beta} does not directly inhibit HNF4, but contributes to its transcriptional regulation by SMAD2/3 recruiting acetyltransferase CBP/p300 to the HNF4 promoter. The recruitment of CBP/p300 is indispensable for C/EBPa binding, another essential requirement for constitutive HNF4 expression in hepatocytes. In contrast to the observed induction of HNF4, SMAD2/3 inhibits C/EBP transcription. Therefore, long-term TGF-{beta} incubation results in C/EBP depletion, which abrogates HNF4 expression. Intriguingly, SMAD2/3 inhibitory binding to the C/EBP promoter is abolished by insulin. Thus, maintaining a high insulin concentration in culture medium ensures constitutive HNF4 and thereby prevents TGF-{beta}-induced hepatocyte EMT. Furthermore, insulin inhibits TGF-{beta}-induced SMAD2/3 binding to the promoters of core EMT transcription factors e.g., SNAI1. SNAI1 transcription requires both SMAD2/3 and FOXO1 in nuclei. Insulin inhibits SNAI1 transcription through impeding SMAD2/3 binding to its promoter and inducing FOXO1 phosphorylation. Hence, insulin is the key factor that prevents TGF-{beta}-induced EMT in hepatocytes.

cell biology↗

bioRxiv2022

Proteomic Landscape of Human Spermatozoa: Optimized Extraction Method and Application

Human spermatozoa proteomics exposed to some physical, biological or chemical stressors is being explored. However, there is a lack of optimized sample preparation methods to achieve in-depth protein coverage for sperm cells. Meanwhile, it is not clear whether antibiotics can regulate proteins to affect sperm quality. Here, we systematically compared a total of six different protein extraction methods based the combination of three commonly used lysis buffers and physical lysis strategies. The urea buffer combined with ultrasonication (UA_ultrasonication) produced the highest protein extraction rate, leading to the deepest coverage of human sperm proteome (5685 protein groups) from healthy human sperm samples. Since the antibiotics, amoxicillin and clarithromycin, have been widely used against H. pylori infection, we conduct a longitudinal study of sperm proteome via data-independent acquisition tandem mass spectrometry (DIA-MS/MS) on an infected patient during on and off therapy with these two drugs. The semen examination and morphological analysis were performed combined with proteomics analysis. Our results indicated that antibiotics may cause an increase in the sperm concentration and the rate of malformed sperm and disrupt proteome expression in sperm. This work provides an optimized extraction method to characterize the in-depth human sperm proteome and to extend its clinical applications.

biochemistry↗

bioRxiv2022

One-Step PCR Amplicon Library Construction (OSPALC, version 1)

High-throughput sequencing of amplicons has been widely used to precisely and efficiently identify species compositions and analyze community structures, greatly promoting biological studies involving large amounts of complex samples, especially those involving environmental and pathogen-monitoring ones. However, commercial library preparation kits for amplicon sequencing, which generally require multiple steps, including adapter ligation and indexing, are expensive and time-consuming, especially for applications at a large scale. Here, to overcome this technical hurdle, we present a one-step PCR amplicon library construction (OSPALC) protocol for amplicon library preparations in the lab along with a QIIME2-based amplicon analysis pipeline. High-quality reads have been generated by this approach to reliably identify species compositions of mock bacterial communities and environmental samples. With this protocol, the amplicon library construction is completed through one regular PCR with long primers, and the total cost per DNA/cDNA sample decreases to just 1/15 of the typical cost via service providers. Empirically tested primers to construct OSPALC libraries for 16S rDNA V4 regions are demonstrated as a case study. Criteria to design primers targeting at any regions of prokaryotic and eukaryotic genomes are also suggested. In principle, OSPALC can be conveniently used in amplicon library constructions of any target gene of both prokaryotes and eukaryotes at the DNA or RNA levels, and will facilitate research in numerous fields.

genomics↗

bioRxiv2022

Dissecting aneuploidy phenotypes by constructing Sc2.0 chromosome VII and SCRaMbLEing synthetic disomic yeast

Aneuploidy compromises genomic stability, often leading to embryo inviability, and is frequently associated with tumorigenesis and aging. Different aneuploid chromosome stoichiometries lead to distinct transcriptomic and phenotypic changes, making it helpful to study aneuploidy in tightly controlled genetic backgrounds. By deploying the engineered SCRaMbLE system to the newly synthesized Sc2.0 megabase chromosome VII (synVII), we constructed a synthetic disomic yeast and screened hundreds of SCRaMbLEd derivatives with diverse chromosomal rearrangements. Phenotypic characterization and multi-omics analysis revealed that fitness defects associated with aneuploidy could be restored by i) removing most of the chromosome content, or ii) modifying specific regions in the duplicated chromosome. These findings indicate that both chromosome copy number and chromosomal regions contribute to the aneuploidy-related phenotypes, and the synthetic yeast resource opens new paradigms in studying aneuploidy. In briefUse of SCRaMbLE and newly synthesized Mb-scale Sc2.0 chromosome VII enables insights into genotype/phenotype relationships associated with aneuploidy HighlightsO_LIDe novo design and synthesis of a Mb-scale synthetic yeast chromosome VII, carrying 11.8% sequence modifications and representing nearly 10% of the yeast genome. C_LIO_LIA disomic yeast (n + synVII) is constructed for dissecting the aneuploidy phenotype C_LIO_LISCRaMbLE enables systematic exploration of regions causing aneuploidy phenotypes C_LIO_LIChromosomal copy number and content both contribute to aneuploidy phenotypes C_LIO_LIA 20 Kb deletion on the right arm of synVII leads to fitness improvement linked to up-regulation of protein synthesis C_LI

synthetic biology↗

bioRxiv2022

Genetic regulation of the human plasma proteome in 54,306 UK Biobank participants

The UK Biobank Pharma Proteomics Project (UKB-PPP) is a collaboration between the UK Biobank (UKB) and thirteen biopharmaceutical companies characterising the plasma proteomic profiles of 54,306 UKB participants. Here, we describe results from the first phase of UKB-PPP, including protein quantitative trait loci (pQTL) mapping of 1,463 proteins that identifies 10,248 primary genetic associations, of which 85% are newly discovered. We also identify independent secondary associations in 92% of cis and 29% of trans loci, expanding the catalogue of genetic instruments for downstream analyses. The study provides an updated characterisation of the genetic architecture of the plasma proteome, leveraging population-scale proteomics to provide novel, extensive insights into trans pQTLs across multiple biological domains. We highlight genetic influences on ligand-receptor interactions and pathway perturbations across a diverse collection of cytokines and complement proteins, and illustrate long-range epistatic effects of ABO blood group and FUT2 secretor status on proteins with gastrointestinal tissue-enriched expression. We demonstrate the utility of these data for drug target discovery by extending the genetic proxied effect of PCSK9 levels on lipid concentrations, cardio- and cerebro-vascular diseases, and additionally disentangle specific genes and proteins perturbed at COVID-19 susceptibility loci. This public-private partnership provides the scientific community with an open-access proteomics resource of unprecedented breadth and depth to help elucidate biological mechanisms underlying genetic discoveries and accelerate the development of novel biomarkers and therapeutics.

genetics↗

bioRxiv2022

Cross regulation between the molecular clock and kidney inflammatory, metabolic and fibrotic responses

Chronic kidney disease is a highly prevalent condition that remains a major clinical and biomedical challenge. Tubulo-interstitial fibrosis is the common pathological substrate for many causes that lead to chronic kidney disease. It is characterized by profound derangements in metabolic and inflammatory responses, whereby functional tissue is replaced with extracellular matrix, leading to the suppression of renal function. Perturbations in the circadian rhythm have been associated with many human pathologies, including renal disease. However, the role of the molecular clock in the instauration of fibrosis remains incompletely understood. We investigated the relationship between the molecular clock and renal damage in experimental models of injury and fibrosis (UUO, FAN and adenine toxicity), employing genetically-modified mice with selective deficiencies of the clock components Bmal1, Clock and Cry. We found that UUO induced a marked increase in the expression of Bmal1. In human tubular epithelial cells, the pro-fibrotic mediator, TGF-{beta}, significantly altered the expression of core clock components. We further observed that the absence of Cry drastically aggravated kidney fibrosis, while both Cry and Clock played a role in the neutrophil and macrophage mediated inflammatory response, respectively. Suppression of Cry1/2 was associated with a major shift in the expression of metabolism-related genes, underscoring the importance of metabolic dysfunction in fibrosis. These results support a reciprocal interaction between the circadian clock and the response to kidney injury. Translational statementChronic kidney disease (CKD) is a highly prevalent clinical syndrome that still poses major clinical challenges. Kidney fibrosis underlies many cases of CKD and therapies against it are of very limited efficacy. Alterations in circadian rhythms (CR) are relevant in patients with CKD, but very little is known about the relationship between CKD and CR. Our study shows that disruption of the molecular clock can impact kidney inflammation and fibrosis and that, reciprocally, kidney fibrosis can alter the expression of clock components. A better understanding of this crosstalk could open new therapeutic avenues for the prevention and treatment of CR-related CKD.

physiology↗

bioRxiv2022

Target-agnostic discovery of Rett Syndrome therapeutics by coupling computational network analysis and CRISPR-enabled in vivo disease modeling

Many neurodevelopmental genetic disorders, such as Rett syndrome, are caused by a single gene mutation but trigger changes in expression and regulation of numerous other genes. This severely impair functions of multiple organs and organ systems beyond the central nervous system (CNS), adding to the challenge of developing broadly effective treatments based on a single drug target. This challenge is further complicated by the lack of sufficiently broad and biologically relevant drug screens, and the inherent complexity in identifying clinically relevant targets responsible for diverse phenotypes. Here, we combined human gene regulatory network-based computational drug prediction with in vivo screening in a population-level diversity, CRISPR-edited, Xenopus laevis tadpole model of Rett syndrome to carry out target-agnostic drug discovery, which rapidly led to the identification of the FDA-approved drug vorinostat as a potential repurposing candidate. Vorinostat broadly improved both CNS and non-CNS (e.g., gastrointestinal, respiratory, inflammatory) abnormalities in a pre-clinical mouse model of Rett syndrome. This is the first Rett syndrome treatment to demonstrate pre-clinical efficacy across multiple organ systems when dosed after the onset of symptoms, and network analysis revealed a putative therapeutic mechanism for its cross-organ normalizing effects based on its impact on acetylation metabolism and post-translational modifications of microtubules. Although traditionally considered an inhibitor of histone deacetylases (HDAC), vorinostat unexpectedly restored protein acetylation across both hypo- and hyperacetylated tissues, suggesting non-HDAC-mediated therapeutic mechanisms supported by proteomic analysis.

neuroscience↗

bioRxiv2021

An ultrapotent RBD-targeted biparatopic nanobody neutralizes broad SARS-CoV-2 variants

The wide transmission and host adaptation of SARS-CoV-2 have led to the rapid accumulation of mutations, posing significant challenges to the effectiveness of vaccines and therapeutic antibodies. Although several neutralizing antibodies were authorized for emergency clinical use, convalescent patients derived natural antibodies are vulnerable to SARS-CoV-2 Spike mutation. Here, we describe the screen of a panel of SARS-CoV-2 receptor-binding domain (RBD) targeted nanobodies (Nbs) from a synthetic library and the design of a biparatopic Nb, named Nb1-Nb2, with tight affinity and super wide neutralization breadth against multiple SARS-CoV-2 variants of concern. Deep-mutational scanning experiments identify the potential binding epitopes of the Nbs on the RBD and demonstrate that biparatopic Nb1-Nb2 has a strong escape resistant feature against more than 60 tested RBD amino acid substitutions. Using pseudovirion-based and trans-complementation SARS-CoV-2 tools, we determine that the Nb1-Nb2 broadly neutralizes multiple SARS-CoV-2 variants, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), Lambda (C.37), Kappa (B.1.617.1) and Mu (B.1.621). Furthermore, a heavy chain antibody is constructed by fusing the human IgG1 Fc to Nb1-Nb2 (designated as Nb1-Nb2-Fc) to improve its neutralization potency, yield, stability and potential half-life extension. For the new Omicron variant (B.1.1.529) that harbors unprecedented multiple RBD mutations, Nb1-Nb2-Fc keeps a firm affinity (KD < 1.0x10-12 M) and strong neutralizing activity (IC50 = 0.0017 nM). Together, we developed a tetravalent biparatopic human heavy chain antibody with ultrapotent and broad-spectrum SARS-CoV-2 neutralization activity which highlights the potential clinical applications.

microbiology↗

bioRxiv2021

The cerebellum initiates severe tonic-clonic seizures by altering neuronal activity in the ventral posteromedial nucleus (VPM) of the thalamus

Thalamo-cortical networks are central to seizures, yet its unclear how these circuits initiate the seizures. Here, we test the hypothesis that a facial region of the thalamus, the VPM, is a source of convulsive, tonic-clonic seizures. We devised an in vivo optogenetic mouse model to elicit tonic-clonic seizures by driving convergent input to the VPM. With viral tracing, we show dense cerebellar and cerebral cortical afferent input to the VPM. Lidocaine microinfusions into the cerebellar nuclei selectively block seizure initiation. We perform single-unit electrophysiology recordings during awake, convulsive seizures to define the local activity of thalamic neurons before, during, and after seizure onset. We find highly dynamic activity with biphasic properties, raising the possibility that heterogenous activity patterns promote seizures. These data reveal the VPM as a source of tonic-clonic seizures, with cerebellar input providing the predominant signals.

neuroscience↗

bioRxiv2021

A high-continuity and annotated tomato reference genome

Genetic and functional genomics studies require a high-quality genome assembly. Tomato (Solanum lycopersicum), an important horticultural crop, is an ideal model species for the study of fruit development. Here, we assembled an updated reference genome of S. lycopersicum cv. Heinz 1706 that was 799.09 Mb in length, containing 34,384 predicted protein-coding genes and 65.66% repetitive sequences. By comparing the genomes of S. lycopersicum and S. pimpinellifolium LA2093, we found a large number of genomic fragments probably associated with human selection, which may have had crucial roles in the domestication of tomato. Our results offer opportunities for understanding the evolution of the tomato genome and will facilitate the study of genetic mechanisms in tomato biology. Information for the assembled genome SLT1.0 was deposited both into the Genome Warehouse (GWH) database (https://bigd.big.ac.cn/gwh/) in the BIG Data Center under Accession Number GWHBAUD00000000.

genomics↗

bioRxiv2021

UBXN3B Restricts Viral Pathogenesis by Maintaining Hematopoietic Homeostasis

Hematopoiesis is finely regulated to enable timely production of the right numbers and types of mature immune cells to maintain tissue homeostasis. Dysregulated hematopoiesis may compromise antiviral immunity and/or exacerbate immunopathogenesis. Herein, we report an essential role of UBXN3B in maintenance of hematopoietic homeostasis and restriction of immunopathogenesis during respiratory viral infection. Ubxn3b deficient (Ubxn3b-/-) mice are highly vulnerable to SARS-CoV-2 and influenza A infection, characterized by more severe lung immunopathology, lower virus-specific IgG, significantly fewer B cells, but more myeloid cells than Ubxn3b+/+ littermates. This aberrant immune compartmentalization is recapitulated in uninfected Ubxn3b-/- mice. Mechanistically, UBXN3B controls precursor B-I (pre-BI) transition to pre-BII and subsequent proliferation in a cell-intrinsic manner, by maintaining BLNK protein stability and pre-BCR signaling. These results reveal an essential role of UBXN3B for the early stage of B cell development.

immunology↗

bioRxiv2020

Post-transcriptional gene regulation by the RNA binding protein IGF2BP3 is critical for MLL-AF4 mediated leukemogenesis

Despite recent advances in therapeutic approaches, patients with MLL-rearranged leukemia still have poor outcomes and a high risk of relapse. Here, we found that MLL-AF4, the most common MLL fusion protein in patients, transcriptionally induces IGF2BP3 and that IGF2BP3 strongly amplifies MLL-Af4 mediated leukemogenesis. Deletion of Igf2bp3 significantly increases the survival of mice with MLL-Af4 driven leukemia and greatly attenuates disease, with a minimal impact on baseline hematopoiesis. At the cellular level, MLL-Af4 leukemia-initiating cells require Igf2bp3 for their function in leukemogenesis. eCLIP and transcriptome analysis of MLL-Af4 transformed stem and progenitor cells and MLL-Af4 bulk leukemia cells reveals a complex IGF2BP3-regulated post-transcriptional operon governing leukemia cell survival and proliferation. Regulated mRNA targets include important leukemogenic genes such as those in the Hoxa locus and numerous genes within the Ras signaling pathway. Together, our findings show that IGF2BP3 is an essential positive regulator of MLL-AF4 mediated leukemogenesis and represents an attractive therapeutic target in this disease.

cancer biology↗

bioRxiv2020

Deleting Mecp2 from the entire cerebellum rather than its neuronal subtypes causes a delay in motor learning in mice

Rett syndrome is a devastating childhood neurological disorder caused by mutations in MECP2. Of the many symptoms, motor deterioration is a significant problem for patients. In mice, deleting Mecp2 from the cortex or basal ganglia causes motor dysfunction, hypoactivity, and tremor, which are abnormalities observed in patients. However, little is known about the consequences of deleting Mecp2 from the cerebellum, a brain region critical for motor function. Here we show that deleting Mecp2 from the entire cerebellum, but not from individual cerebellar cell types, causes a delay in motor learning that is overcome by additional training. We also observed irregular firing rates of Purkinje cells and transcriptional misregulation within the cerebellum of knockout mice. These findings demonstrate that the motor deficits present in Rett syndrome arise, in part, from cerebellar dysfunction. For Rett syndrome as well as other neurodevelopmental disorders, our results highlight the importance of understanding which brain regions contribute to disease phenotypes.

neuroscience↗

bioRxiv2020

N6-methyladenine DNA demethylase ALKBH1 regulates mammalian axon regeneration

Recent studies have shown that DNA N6-methyladenine (N6-mA) modification is emerging to be a novel and important epigenetic regulator of mammalian gene transcription. Several studies demonstrated DNA N6-mA in human or rodents was regulated by methyltransferase N6AMT1 and demethylase ALKBH1. Moreover, studies in mouse brain or human glioblastoma cells showed that reduced level of N6-mA or higher level of ALKBH1 was correlated with up regulated levels of genes associated with neuronal development. We thus investigated the functional roles of ALKBH1 in sensory axon regeneration. Our results showed that ALKBH1 regulated the level of N6-mA in sensory neurons, and upon peripheral nerve injury ALKBH1 was up regulated in mouse sensory neurons. Functionally, knocking down ALKBH1 in sensory neurons resulted in reduced axon regeneration in vitro and in vivo, which could be rescued by simultaneously knocking down N6AMT1. Moreover, knocking down ALKBH1 led to decreased levels of many neurodevelopment regulatory genes, including neuritin that is well known to enhance axon growth and regeneration. Our study not only revealed a novel physiological function of DNA N6-mA, but also identified a new epigenetic mechanism regulating mammalian axon regeneration. Significance StatementThe study demonstrated that DNA N6-methyladenine (N6-mA) modification played important roles in regulation of sensory axon regeneration, likely through controlling the expression of neurodevelopmental associated genes. The results will add new evidence about the physiological function of DNA N6-mA and its regulatory demethylase ALKBH1 in neurons.

neuroscience↗

bioRxiv2020

Identification of Retinal Ganglion Cell Types and Brain Nuclei expressing the transcription factor Brn3c/Pou4f3 using a Cre recombinase knock-in allele.

Members of the POU4F/Brn3 transcription factor family have an established role in the development of retinal ganglion cell types (RGCs), the projection sensory neuron conveying visual information from the mammalian eye to the brain. Our previous work using sparse random recombination of a conditional knock-in reporter allele expressing Alkaline Phosphatase (AP) and intersectional genetics had identified three types of Pou4f3/Brn3c positive (Brn3c+) RGCs. Here, we describe a novel Brn3cCre mouse allele generated by serial Dre to Cre recombination. We use this allele to explore the expression overlap of Brn3c with Brn3a and Brn3b and the dendritic arbor morphologies and visual stimulus properties of Brn3c+ RGC types. Furthermore, we explore Brn3c-expressing brain nuclei. Our analysis reveals a much larger number of Brn3c+ RGCs and more diverse set of RGC types than previously reported. The majority of RGCs having expressed Brn3c during development are still Brn3c positive in the adult, and all of them express Brn3a while only about half express Brn3b. Intersection of Brn3b and Brn3c expression highlights an area of increased RGC density, similar to an area centralis, corresponding to part of the binocular field of view of the mouse. Brn3c+ neurons and projections are present in multiple brain nuclei. Brn3c+ RGC projections can be detected in the Lateral Geniculate Nucleus (LGN), Pretectal Area (PTA) and Superior Colliculus (SC) but also in the thalamic reticular nucleus (TRN), a visual circuit station that was not previously described to receive retinal input. Most Brn3c+ neurons of the brain are confined to the pretectum and the dorsal midbrain. Amongst theses we identify a previously unknown Brn3c+ subdivision of the deep mesencephalic nucleus (DpMe). Thus, our newly generated allele provides novel biological insights into RGC type classification, brain connectivity and midbrain cytoarchitectonic, and opens the avenue for specific characterization and manipulation of these structures.

neuroscience↗

bioRxiv2020

Evaluation validation of a qPCR curve analysis method and conventional approaches

Real-time quantitative polymerase chain reaction (qPCR) is a sensitive and reliable method for mRNA quantification and rapid analysis of gene expression from a large number of starting templates. It is based on the statistical significance of the beginning of exponential phase in real-time PCR kinetics, reflecting quantitative cycle of the initial target quantity and the efficiency of the PCR reaction (the fold increase of product per cycle). We used the large clinical biomaker dataset and 94-replicates-4-dilutions set which was published previously as research tools, then proposed a new qPCR curve analysis method----CqMAN, to determine the position of quantitative cycle as well as the efficiency of the PCR reaction and applied in the calculations. To verify algorithm performance, 20 genes from biomarker and partial data with concentration gradients from 94-replicates-4-dilutions set of MYCN gene were used to compare various publicly available curve analysis methods with our method and established a suitable evaluation index system. The results show that CqMAN method is comparable to other methods and can be a feasible method which applied to our self-developed qPCR data processing and analysis software, providing a simple tool for qPCR analysis.

biochemistry↗

bioRxiv2020

A critical role for MSR1 in vesicular stomatitis virus infection of the central nervous system

Macrophage scavenger receptor 1 (MSR1) plays an important role in host defense to bacterial infections, M2 macrophage polarization and lipid homeostasis. However, its physiological function in viral pathogenesis remains poorly defined. Herein, we report that MSR1 facilitates vesicular stomatitis virus (VSV) infection in the spinal cord. Msr1-deficient (Msr1-/-) mice presented reduced morbidity and mortality following lethal VSV infection, along with normal viremia and antiviral innate immune responses, compared to Msr1+/- littermates and wild-type mice. Msr1 expression was selectively upregulated in the spinal cord, which was the predominant target of VSV infection. The viral load in the spinal cord was positively correlated with Msr1 expression level and was reduced in Msr1-/- mice. Through its extracellular domain, MSR1 interacted with VSV surface glycoprotein and facilitated its cellular entry. In conclusion, our results demonstrate that MSR1 serves as a cellular entry receptor for VSV and facilitates its infection specifically in the spinal cord.

immunology↗