Biology subjects

Su, S.

Publications and source records attributed to Su, S..

At least 55 records · Page 3Linked to original sources

bioRxiv2023

Metabolism regulates muscle stem cell self-renewal by connecting the microenvironment and histone acetylation

Skeletal muscle contains a resident population of somatic stem cells capable of both self-renewal and differentiation. The signals that regulate this important decision have yet to be fully elucidated. Here we use metabolomics and mass spectrometry imaging (MSI) to identity a state of localized hyperglycaemia following skeletal muscle injury. We show that committed muscle progenitor cells exhibit an enrichment of glycolytic and TCA cycle genes and that extracellular monosaccharide availability regulates intracellular citrate levels and global histone acetylation. Muscle stem cells exposed to a reduced (or altered) monosaccharide environment demonstrate reduced global histone acetylation and transcription of myogenic determination factors (including myod1). Importantly, reduced monosaccharide availability was linked directly to increased rates of asymmetric division and muscle stem cell self-renewal in regenerating skeletal muscle. Our results reveal an important role for the extracellular metabolic environment in the decision to undergo self-renewal or myogenic commitment during skeletal muscle regeneration.

cell biology↗

bioRxiv2023

A Series of Composited Tumor DNA Reference Materials Containing Three Genes and Ten Mutation Positions for CNV and SNV Detection

Processes in clinic for tumors diagnosis and treatment need reference materials (RMs) to evaluate and calibrate. However, no RMs can provides properties of copy number variation (CNV) and single nucleotide variants (SNV) of genes EGFR, HER2, MET, PIK3CA, KRAS, BRAF, NRAS simultaneously. In this study, we used commercial cell lines to construct a series of tumor RMs containing property mentioned above. Furthermore, we evaluated their stability, homogeneity, and commutability by droplet digital PCR and next generation sequencing technology. The results showed that, for tumor CNV gDNA RM, the copy number is 7.3 copies/L (EGFR), 5.3 copies/L (HER2) and 8.2 copies/L (MET). For tumor 5% SNV gDNA RM, the mutation frequency of each mutation position showed as follow: EGFR-E746A750 (24.6%), EGFR-L858R (5.8%), EGFR-T790M (5.5%), EGFR-G719S (6.6%), PIK3CA-E545K (4.7%), PIK3CA-H1047R (5.8%), KRAS-G13D (8.2%), KRAS-G12D (6.5%), BRAF-V600E (4.6%), NRAS-Q61K (8.5%). All variable coefficient (CV) of tumor gDNA RM for homogeneity were less than 7%, that of CNV+SNV ctDNA RM were less than 17%. Besides, the CV for commutability of the all types of RMs were less than 17%. These RMs can be applied into a wide range type of sequencing panels and provides a closer simple background.

molecular biology↗

bioRxiv2023

Enhanced in Vivo Blood Brain Barrier Transcytosis of Macromolecular Cargo Using an Engineered pH-sensitive Mouse Transferrin Receptor Binding Nanobody

BackgroundThe blood brain barrier limits entry of macromolecular diagnostic and therapeutic cargos. Blood brain barrier transcytosis via receptor mediated transport systems, such as the transferrin receptor, can be used to carry macromolecular cargos with variable efficiency. Transcytosis involves trafficking through acidified intracellular vesicles, but it is not known whether pH-dependent unbinding of transport shuttles can be used to improve blood brain barrier transport efficiency. MethodsA mouse transferrin receptor binding nanobody, NIH-mTfR-M1, was engineered to confer greater unbinding at pH 5.5 vs 7.4 by introducing multiple histidine mutations. The histidine mutant nanobodies were coupled to neurotensin for in vivo functional blood brain barrier transcytosis testing via central neurotensin-mediated hypothermia in wild-type mice. Multi-nanobody constructs including the mutant M1R56H, P96H, Y102H and two copies of the P2X7 receptor-binding 13A7 nanobody were produced to test proof-of-concept macromolecular cargo transport in vivo using quantitatively verified capillary depleted brain lysates and in situ histology. ResultsThe most effective histidine mutant, M1R56H, P96H, Y102H -neurotensin, caused >8{degrees}C hypothermia after 25 nmol/kg intravenous injection. Levels of the heterotrimeric construct M156,96,102His-13A7-13A7 in capillary depleted brain lysates peaked at 1 hour and were 60% retained at 8 hours. A control construct with no brain targets was only 15% retained at 8 hours. Addition of the albumin-binding Nb80 nanobody to make M1R56H, P96H, Y102H -13A7-13A7-Nb80 extended blood half-life from 21 minutes to 2.6 hours. At 30-60 minutes, biotinylated M1R56H, P96H, Y102H -13A7-13A7-Nb80 was visualized in capillaries using in situ histochemistry, whereas at 2-16 hours it was detected in diffuse hippocampal and cortical cellular structures. Levels of M1R56H, P96H, Y102H-13A7-13A7-Nb80 reached more than 3.5 percent injected dose/gram of brain tissue after 30 nmol/kg intravenous injection. However, higher injected concentrations did not result in higher brain levels, compatible with saturation and an apparent substrate inhibitory effect. ConclusionThe pH-sensitive mouse transferrin receptor binding nanobody M1R56H, P96H, Y102H may be a useful tool for rapid and efficient modular transport of diagnostic and therapeutic macromolecular cargos across the blood brain barrier in mouse models. Additional development will be required to determine whether this nanobody-based shuttle system will be useful for imaging and fast-acting therapeutic applications.

neuroscience↗

bioRxiv2023

Metabolic Reprogramming via targeting ACOD1 promotes polarization and anti-tumor activity of human CAR-iMACs in solid tumors

The pro-inflammatory state of macrophages is crucial in conferring its role in combating tumor cells. That state is closely associated with metabolic reprogramming. Here we identified key metabolic genes regulating macrophage pro-inflammatory activation in a pooled metabolic gene knockout CRISPR screen. We found that KEAP1 and ACOD1 are strong regulators of the pro-inflammatory state, and therefore developed human ACOD1 knockout macrophages with our induced pluripotent stem cell-derived CAR-macrophage (CAR-iMAC) platform. The engineered iMACs showed stronger and more persistent polarization toward the pro-inflammatory state, more ROS production, and more potent phagocytosis and cytotoxic functions against cancer cells in vitro. Upon transplantation to ovarian or pancreatic cancer mouse models, ACOD1 depleted CAR-iMACs exhibited enhanced capacity in repressing tumors in vivo and prolonged the lifespan of mice. In addition, combining ACOD1-depleted CAR-iMACs with immune check point inhibitors (ICIs), such as the anti-CD47 antibody or anti-PD1 antibody resulted in stronger tumor suppressing effect. Mechanistically, the depletion of ACOD1 reduced the immunometabolite itaconate, allowing KEAP1 to prevent NRF2 from entering the nucleus to activate the anti-inflammatory program. This study demonstrates that ACOD1 is a new myeloid target for cancer immunotherapy and metabolically engineered human iPSC-derived CAR-iMACs exhibit enhanced polarization and anti-tumor functions in adoptive cell transfer therapies.

immunology↗

bioRxiv2023

BATF relieves hepatic steatosis by inhibiting PD1 and promoting energy metabolism

The rising prevalence of nonalcoholic fatty liver disease (NAFLD) has become a global health threat that needs to be addressed urgently. Basic leucine zipper ATF-like transcription factor (BATF) is commonly thought to be involved in immunity, but its effect on lipid metabolism is not clear. Here, we investigated the function of BATF in hepatic lipid metabolism. BATF alleviated high-fat diet (HFD)-induced hepatic steatosis and inhibited elevated programmed cell death protein (PD)1 expression induced by HFD. A mechanistic study confirmed that BATF regulated fat accumulation by inhibiting PD1 expression and promoting energy metabolism. PD1 antibodies alleviated hepatic lipid deposition. In conclusion, we identified the regulatory role of BATF in hepatic lipid metabolism and that PD1 is a target for alleviation of NAFLD. This study provides new insights into the relationship between BATF, PD1 and NAFLD.

molecular biology↗

bioRxiv2022

ExposomeX: Integrative Exposomic Platform Expediates Discovery of "Exposure-Biology-Disease" Nexus

Exposome has become the hotspot of next-generation health studies. To date, there is no available effective platform to standardize the analysis of exposomic data. In this study, we aim to propose one new framework of exposomic analysis and build up one novel integrated platform "ExposomeX" to expediate the discovery of the "Exposure-Biology-Disease" nexus. We have developed 13 standardized modules to accomplish six major functions including statistical learning (E-STAT), exposome database search (E-DB), mass spectrometry data processing (E-MS), meta-analysis (E-META), biological link via pathway integration and protein-protein interaction (E-BIO) and data visualization (E-VIZ). Using ExposomeX, we can effectively analyze the multiple-dimensional exposomics data and investigate the "Exposure-Biology-Disease" nexus by exploring mediation and interaction effects, understanding statistical and biological mechanisms, strengthening prediction performance, and automatically conducting meta-analysis based on well-established literature databases. The performance of ExposomeX has been well validated by re-analyzing two previous multi-omics studies. Additionally, ExposomeX can efficiently help discover new associations, as well as relevant in-depth biological pathways via protein-protein interaction and gene ontology network analysis. In sum, we have proposed a novel framework for standardized exposomic analysis, which can be accessed using both R and online interactive platform (http://www.exposomex.cn/).

bioinformatics↗

bioRxiv2022

A non-invasive, fast on/off 'Odourgenetic' Method to Manipulate Physiology

Manipulating molecular processes governing physiological functions has significant potential for clinical therapeutics and is an important approach to elucidate the cellular basis of physiological functions. Here, we designed a Odourgenetic system co-expressed Drosophila odorant receptor system (DORs) consisting of OR35a and OR83b, which were exclusively activated by their odor ligand, 2-pentanone. Applying 2-pentanone to DOR-expressing cells or tissues induced calcium influx and membrane depolarization. By inhalation of 2-pentanone, we successfully applied DORs to manipulate behaviour, control insulin secretion and regulate blood glucose and manipulate muscle contraction and associated limb movement. Because 2-pentanone rapidly enters the blood upon inhalation and leaves the body by exhalation, this odorant can be used with DORs to manipulate cellular function, and the manipulation can be terminated at any time. Such feature approach significantly improves the safety and controllability of DORs used in the clinic. Thus, the present study developed a non-invasive, controllable, fast on/off method to manipulate cellular activity and behaviour on a time scale of minutes.

cell biology↗

bioRxiv2022

VLA-4 suppression by senescence signals regulates meningeal immunity and leptomeningeal metastasis

Leptomeningeal metastasis is associated with dismal prognosis and has few treatment options. However, very little is known about the immune response to leptomeningeal metastasis. Here, by establishing an immunocompetent mouse model of breast cancer leptomeningeal metastasis, we found that tumor-specific CD8+ T cells were generated in deep cervical lymph nodes (dCLNs) and played an important role in controlling leptomeningeal metastasis. Mechanistically, T cells in dCLNs displayed a senescence phenotype and their recruitment was impaired in mice bearing cancer cells that preferentially colonized in leptomeningeal space. Upregulation of p53 suppressed the transcription of VLA-4 in senescent dCLN T cells and consequently inhibited their migration to the leptomeningeal compartment. Clinically, CD8+ T cells from cerebrospinal fluid of patients with leptomeningeal metastasis exhibited senescence and VLA-4 downregulation. Collectively, our findings demonstrated that CD8+ T cell immunosenescence drives leptomeningeal metastasis.

immunology↗

bioRxiv2022

Tumor removal limits prostate cancer cell dissemination in bone cortex and osteoblasts induce cancer cell dormancy

BackgroundDisseminated tumor cells (DTCs) can enter a dormant state and cause no symptoms in cancer patients. On the other hand, the dormant DTCs can reactivate and cause metastases progression and lethal relapses. In prostate cancer (PCa), relapse can happen after curative treatments such as primary tumor removal. The impact of surgical removal on PCa dissemination and dormancy remains elusive. Furthermore, as dormant DTCs are asymptomatic, dormancy-inducing can be an operational cure for preventing metastases and relapse of PCa patients. MethodsWe used a PCa subcutaneous xenograft model and species-specific PCR to survey the DTCs in various organs at different time points of tumor growth and in response to tumor removal. We developed in vitro 2D and 3D co-culture models to recapitulate the dormant DTCs in the bone microenvironment. Proliferation assays, fluorescent cell cycle reporter, qRT-PCR, and Western Blot were used to characterize the dormancy phenotype. We performed RNA sequencing to determine the dormancy signature of PCa. A drug repurposing algorithm was applied to predict dormancy-inducing drugs and a top candidate was validated for the efficacy and the mechanism of dormancy induction. ResultsWe found DTCs in almost all mouse organs examined, including bones, at week 2 post-tumor cell injections. Surgical removal of the primary tumor reduced the overall DTC abundance, but the DTCs were enriched only in the bones. We found that osteoblasts, but not other cells of the bones, induced PCa cell dormancy. RNA-Seq revealed the suppression of mitochondrial-related biological processes in osteoblast-induced dormant PCa cells. Importantly, the mitochondrial-related biological processes were found up-regulated in both circulating tumor cells and bone metastases from PCa patients data. We predicted and validated the dormancy-mimicking effect of PF-562271, an inhibitor of focal adhesion kinase (FAK) in vitro. Decreased FAK phosphorylation and increased nuclear translocation were found in both co-cultured and PF-271-treated C4-2B cells, suggesting that FAK plays a key role in osteoblast-induced PCa dormancy. ConclusionsOur study provides the first insights into how primary tumor removal enriches PCa cell dissemination in the bones, defines a unique osteoblast-induced PCa dormancy signature, and identifies FAK as a PCa cell dormancy gatekeeper.

cancer biology↗

bioRxiv2022

Neuronal C-Reactive Protein Mediates Neuropathic Pain by Activating Nociceptive FcγRI-Coupled Signaling

BackgroundNeuropathic pain is difficult to treat in clinical practice, and the underlying mechanisms are insufficiently elucidated. Previous studies have demonstrated that Fc{gamma} receptor I (Fc{gamma}RI) is expressed in the neurons of the dorsal root ganglion (DRG) and may be involved in chronic pain. MethodsChronic constriction injury (CCI) was used to induce neuropathic pain in rats. Primary neuron-specific Fcgr1 conditional knockout (CKO) rats were established by crossing rats carrying a Fcgr1loxP+/+ with the PirtCRE+ line. Behavioral and molecular studies were conducted to evaluate the differences between wild-type and CKO rats after CCI. ResultsWe first revealed that CCI activated neuronal Fc{gamma}RI-related signaling in the DRG. CCI-induced neuropathic pain was alleviated in CKO rats. C-reactive protein (CRP) was increased in the DRG after nerve injury. Intraganglionic injection or overexpression of the recombinant CRP protein in the DRG evoked pain accompanied and activated neuronal Fc{gamma}RI. CRP-evoked pain was significantly reduced in CKO rats. Furthermore, microinjection of native IgG into the DRG alleviated neuropathic pain and the activation of neuronal Fc{gamma}RI-related signaling. ConclusionsOur results indicate that the activation of neuronal CRP/Fc{gamma}RI-related signaling plays an important role in the development of pain in CCI. Our findings may provide novel insights into the neuroimmune responses after peripheral nerve injury and might suggest potential therapeutic targets for neuropathic pain.

neuroscience↗

bioRxiv2022

A Small Subset of Cytosolic dsRNAs Must Be Edited by ADAR1 to Evade MDA5-Mediated Autoimmunity

The innate immune system detects viral infection via pattern recognition receptors and induces defense reactions such as production of type I interferon1. One such receptor, MDA5, is activated upon the recognition of double-stranded RNAs (dsRNAs) that are often produced during viral replication2. Endogenous dsRNAs evade MDA5 activation through RNA editing by ADAR1, thus preventing autoimmunity3-5. Among the large number of endogenous dsRNAs, the key substrates whose editing is critical to evade MDA5 activation (termed as immunogenic dsRNAs) remain elusive. Here we reveal the identity of human immunogenic dsRNAs, a surprisingly small fraction of all cellular dsRNAs, to fill the gap in the ADAR1-dsRNA-MDA5 axis. We found that, in contrast to previous findings6,7, the immunogenic dsRNAs were highly enriched in mRNAs and depleted of introns, an expected indication of bona fide substrates of cytosolic MDA5. The immunogenic dsRNAs, in contrast to non-immunogenic dsRNAs, tended to have shorter loop between the stems, which may facilitate dsRNA formation. They also tended to be enriched at the GWAS signals of common inflammatory diseases, implying that they are truly immunogenic. We validated the MDA5-dependent immunogenicity of the dsRNAs, which was dampened following ADAR1-mediated RNA editing. We anticipate that a focused analysis of immunogenic dsRNAs will greatly facilitate the understanding and treatment of cancer and inflammatory diseases in which the important roles of dsRNA editing and sensing continue to be revealed8-13.

genetics↗

bioRxiv2022

ADOLESCENT EXPOSURE TO LOW-DOSE THC DISRUPTS ENERGY BALANCE AND ADIPOSE ORGAN HOMEOSTASIS IN ADULTHOOD

One of cannabis most iconic effects is the stimulation of hedonic high-calorie eating - the munchies - yet habitual cannabis users are on average leaner than non-users. We asked whether this unexpected phenotype might result from lasting changes in energy balance established during adolescence, when habitual use of the drug often begins. We found that daily low-dose administration of cannabis intoxicating constituent, {Delta}9-tetrahydrocannabinol (THC), to adolescent mice causes an adult metabolic phenotype characterized by reduced fat mass, increased lean mass and utilization of fat as fuel, partial resistance to diet-induced obesity and dyslipidemia, and enhanced thermogenesis. Multi-omics analyses revealed that this phenotype is associated with multiple molecular anomalies in the adipose organ, which include ectopic overexpression of muscle-associated proteins and heightened anabolic processing. Thus, adolescent exposure to THC may promote an enduring pseudo-lean state that superficially resembles healthy leanness but might in fact be rooted in adipose organ dysfunction.

pharmacology and toxicology↗

bioRxiv2022

A single cell spatial temporal atlas of skeletal muscle reveals cellular neighborhoods that orchestrate regeneration and become disrupted in aging

Our mobility requires muscle regeneration throughout life. Yet our knowledge of the interplay of cell types required to rebuild injured muscle is lacking, because most single cell assays require tissue dissociation. Here we use multiplexed spatial proteomics and neural network analyses to resolve a single cell spatiotemporal atlas of 34 cell types during muscle regeneration and aging. This atlas maps interactions of immune, fibrogenic, vascular, nerve, and myogenic cells at sites of injury in relation to tissue architecture and extracellular matrix. Spatial pseudotime mapping reveals sequential cellular neighborhoods that mediate repair and a nodal role for immune cells. We confirm this role by macrophage depletion, which triggers formation of aberrant neighborhoods that obstruct repair. In aging, immune dysregulation is chronic, cellular neighborhoods are disrupted, and an autoimmune response is evident at sites of denervation. Our findings highlight the spatial cellular ecosystem that orchestrates muscle regeneration, and is altered in aging. HighlightsO_LISingle cell resolution spatial atlas resolves a cellular ecosystem of 34 cell types in multicellular neighborhoods that mediate efficient skeletal muscle repair C_LIO_LIHighly multiplexed spatial proteomics, neural network and machine learning uncovers temporal dynamics in the spatial crosstalk between immune, fibrogenic, vascular, nerve, and muscle stem cells and myofibers during regeneration C_LIO_LISpatial pseudotime mapping reveals coherent formation of multicellular neighborhoods during efficacious repair and the nodal role of immune cells in coordinating muscle repair C_LIO_LIIn aged muscle, cellular neighborhoods are disrupted by a chronically inflamed state and autoimmunity C_LI

cell biology↗

bioRxiv2022

Selection of Single Domain Anti-Transferrin Receptor Antibodies for Blood-Brain Barrier Transcytosis Using a Neurotensin Based Assay and Histological Assessment of Target Engagement in a Mouse Model of Alzheimer's Disease-Related Amyloid-Beta Pathology

The blood-brain barrier (BBB) presents a major obstacle in developing specific diagnostic imaging agents for many neurological disorders. In this study we aimed to generate single domain anti-mouse transferrin receptor antibodies (anti-mTfR VHHs) to mediate BBB transcytosis as components of novel MRI molecular contrast imaging agents. Anti-mTfR VHHs were produced by immunizing a llama with mTfR, generation of a VHH phage display library, immunopanning, and in vitro characterization of candidates. Site directed mutagenesis was used to generate additional variants. VHH fusions with neurotensin (NT) allowed rapid, hypothermia-based screening for VHH-mediated BBB transcytosis in wild-type mice. One anti-mTfR VHH variant was fused with an anti-amyloid-beta (A{beta}) VHH dimer and labeled with fluorescent dye for direct assessment of in vivo target engagement in a mouse model of AD-related A{beta} plaque pathology. An anti-mTfR VHH called M1 and variants had binding affinities to mTfR of <1nM to 1.52nM. The affinity of the VHH binding to mTfR correlated with the efficiency of the VHH-NT induced hypothermia effects after intravenous injection of 600 nmol/kg body weight, ranging from undetectable for nonbinding mutants to -6{degrees}C for the best mutants. The anti-mTfR VHH variant M1P96H with the strongest hypothermia effect was fused to the anti-A{beta} VHH dimer and labeled with Alexa647; the dye-labeled VHH fusion construct still bound both mTfR and A{beta} plaques. However, after intravenous injection at 600 nmol/kg body weight into APP/PS1 transgenic mice, there was no detectible labeling of plaques above control levels. Thus, NT-induced hypothermia did not correlate with direct target engagement in cortex. There was a surprising dissociation between NT-induced hypothermia, presumably mediated by hypothalamus, and direct engagement with A{beta}-plaques in cortex. Alternative methods to assess anti-mTfR VHH BBB transcytosis will need to be developed for anti-mTfR VHH screening and the development of novel MRI molecular contrast agents.

neuroscience↗

bioRxiv2022

A re-emerging arbovirus in livestock in China: Early genomic surveillance and phylogeographic analysis

Viruses in livestock represent a great risk to public health due to the close contact of their hosts with humans and the potential long-range transportation though animal trade. Here, we show how to predict outbreaks of potential zoonotic pathogens and use spatially-explicit phylogeographic and phylodynamic approaches to provide estimates of key epidemiological parameters. First, we use metagenomic next generation sequencing (mNGS) to identify a Getah virus (GETV) as the pathogen responsible for a re-emerging swine disease in China. The GETV isolate is able to replicate in a variety of cell lines including human cells and shows high pathogenicity in a mouse model suggesting a potential public health risk. We obtained 16 complete genomes and 78 E2 gene sequences from viral strains collected within China from 2017 to 2021 through large-scale surveillance among livestock, pets and mosquitoes. Moreover, phylogenetic analysis reveals that three major GETV lineages are responsible for the current epidemic in livestock in China. We identify three potential positively selected sites and mutations of interest in E2, which may impact the transmissibility and pathogenicity of the virus. We then reconstruct the evolutionary and dispersal history of the virus and test the impact of several environmental factors on the viral genetic diversity through time and on the dispersal dynamic of viral lineages. Of note, we identify temporal variation in livestock meat consumption as a main predictor of viral genetic diversity through time. Finally, phylogeographic analyses indicate that GETV preferentially circulates within areas associated with relatively higher mean annual temperature and pig population density. Our results highlight the importance of continuous surveillance of GETV among livestock in southern Chinese regions associated with relatively high temperatures, and the need to control mosquitoes in the livestock farms. Our analyses of GETV also provide a baseline for future studies of the molecular epidemiology and early warning of emerging arboviruses in China.

evolutionary biology↗

bioRxiv2022

An intergeneric recombinant geminivirus causes soybean stay-green disease

Soybean is one of the most valuable legume crops in the world with high nutritional value. Recently, the outbreak of soybean stay-green syndrome has swept the soybean production in the Huang-Huai-Hai region of China, resulting in huge yield losses, which has become an epidemic and prominent problem in soybean production. However, the cause of the stay-green syndrome remains obscure. Here, we report a novel intergeneric recombinant geminivirus which causes soybean stay-green symptoms. Viral small RNA-based screening identified a new recombinant geminvirus from field soybean stay-green samples. The complete genome sequence of the virus contains 2762 nucleotide (nt) and appears to be an intergeneric recombinant virus in which protein coding for coat protein (V1) is similar to member of genus Mastrevirus, whereas proteins coding for V2, C2, C3 are most similar to those of viruses in the Maldovirus genus, and C1 and C4 are most similar to virus in genus Begomovirus. Inoculation of the infectious clone of the recombinant geminivirus through Agrobacterium rhizogenes causes typical soybean stay-green syndrome which resembles field symptoms including delayed leaf senescence, flat pods and abnormal seeds. The recombinant geminivirus can be detected in seed coat but not in cotyledon and embryo, thus failing to be transmitted by seeds. Moreover, the genome variation and epidemiological dynamic analysis were also carried out to help the continuous epidemiological surveillance of this emerging geminivirus. Collectively, this new geminivirus is tentatively named soybean stay-green associated virus (SoSGV). Our determination of the causal agent of soybean stay-green disease will bolster efforts to develop effective management strategies to control this prevalent disease in the field.

microbiology↗

bioRxiv2021

Single-cell profiling of healthy human kidney reveals features of sex-based transcriptional programs and tissue-specific immunity

Maintaining organ homeostasis requires complex functional synergy between distinct cell types, a snapshot of which is glimpsed through the simultaneously broad and granular analysis provided by single-cell atlases. Knowledge of the transcriptional programs underpinning the complex and specialized functions of human kidney cell populations at homeostasis is limited by difficulty accessing healthy, fresh tissue. Here, we present a single-cell perspective of healthy human kidney from 19 living donors, with equal contribution from males and females, profiling the transcriptome of 27677 high-quality cells to map healthy kidney at high resolution. Our sex-balanced dataset revealed sex-based differences in gene expression within proximal tubular cells, specifically, increased anti-oxidant metallothionein genes in females and the predominance of aerobic metabolism-related genes in males. Functional differences in metabolism were confirmed between male and female proximal tubular cells, with male cells exhibiting higher oxidative phosphorylation and higher levels of energy precursor metabolites. Within the immune niche, we identified kidney-specific lymphocyte populations with unique transcriptional profiles indicative of kidney-adapted functions and validated findings by flow cytometry. We observed significant heterogeneity in resident myeloid populations and identified an MRC1+ LYVE1+ FOLR2+ C1QC+ population as the predominant myeloid population in healthy kidney. This study provides a detailed cellular map of healthy human kidney, revealing novel insights into the complexity of renal parenchymal cells and kidney-resident immune populations.

immunology↗

bioRxiv2021

Total virome characterizations of game animals in China reveals a spectrum of emerging viral pathogens

Game animals are wildlife species often traded and consumed as exotic food, and are potential reservoirs for SARS-CoV and SARS-CoV-2. We performed a meta-transcriptomic analysis of 1725 game animals, representing 16 species and five mammalian orders, sampled across China. From this we identified 71 mammalian viruses, with 45 described for the first time. Eighteen viruses were considered as potentially high risk to humans and domestic animals. Civets (Paguma larvata) carried the highest number of potentially high risk viruses. We identified the transmission of Bat coronavirus HKU8 from a bat to a civet, as well as cross-species jumps of coronaviruses from bats to hedgehogs and from birds to porcupines. We similarly identified avian Influenza A virus H9N2 in civets and Asian badgers, with the latter displaying respiratory symptoms, as well as cases of likely human-to-wildlife virus transmission. These data highlight the importance of game animals as potential drivers of disease emergence. HighlightsO_LI1725 game animals from five mammalian orders were surveyed for viruses C_LIO_LI71 mammalian viruses were discovered, 18 with a potential risk to humans C_LIO_LICivets harbored the highest number of potential high risk viruses C_LIO_LIA species jump of an alphacoronavirus from bats to a civet was identified C_LIO_LIH9N2 influenza virus was detected in a civet and an Asian badger C_LIO_LIHumans viruses were also identified in game animals C_LI

zoology↗