Biology subjects

Duan, Y.

Publications and source records attributed to Duan, Y..

At least 91 records · Page 5Linked to original sources

bioRxiv2022

Role of MULE activities in the positive selection of sweet orange cultivars

Sweet orange (SWO) has one of the largest numbers of cultivar groups in Citrus with diverse horticultural traits just through asexual breeding. However, the molecular mechanism driving its fast selection and diversification is unclear. In this study, we completely surveyed the transposon activities in SWO genomes and unraveled six transposon families with up to 8,974.2-fold activity increase in modern SWO cultivars. Based on the transposon insertion phylogenetic tree, we inferred that modern SWOs date back to a common ancestor [~]500 years ago and reconstructed three major spread events in SWO cultivation history. Activation, acceleration, and silencing of the six families have recurred in distinct lineages. Their insertions are presented as tag mutations for all SWO cultivar groups and can distinguish over 99% of all analyzed SWO accessions. The insertions are enriched in impacting plant development and hormone signaling. This study demonstrated the importance of transposon activities in asexual breeding.

genetics↗

bioRxiv2022

Balancing activation and costimulation of CAR tunes signaling dynamics and enhances therapeutic potency

BackgroundPrimary human T cells engineered with chimeric antigen receptors (CARs) ex vivo can be adoptively transferred to treat cancer. CD19-targeting CAR with CD28 costimulatory domain and CD3{zeta} activation domain have been approved by the US FDA for treating B cell malignancies. MethodsHere we generated mutation of immunorecpetor tyrosine-based activation motifs (ITAMs) in CD3{zeta}, namely 1XX CAR, which altered the balance of activation and costimulation. Next we investigated whether 1XX design could enhance therapeutic potency against solid tumors. We constructed both CD19- and AXL-specific 1XX CARs and compared their in vitro and in vivo functions with their WT counterparts. ResultsEven though 1XX CARs decreased cytotoxicity against tumor cells in vitro, they showed better anti-tumor efficacy in both pancreatic and melanoma mouse models. Detailed analysis revealed that 1XX CAR-T cells proliferated more in response to antigen stimulation in vitro, persisted longer in vivo and had higher percentage of central memory cells. As 1XX modification directly calibrates CAR activation potential, we utilized fluorescence resonance energy transfer (FRET)-based biosensor to monitor signaling dynamics downstream of CARs. Decreased ITAM numbers in 1XX resulted in similar ZAP70 activation, while 1XX induced higher Ca2+ elevation and faster Erk activation than WT CAR, which may contribute to the better therapeutic potency of 1XX. ConclusionsOur results established the surpiosity of 1XX against two targets in different solid tumor models and shed light on the underlying molecular mechanism of CAR signaling, paving the way for the clinical application of 1XX CARs against solid tumors.

immunology↗

bioRxiv2022

Lysine acetylation regulates antibiotic resistance in Escherichia coli

Antibiotic resistance is increasingly becoming a serious challenge to public health. The regulation of metabolism by post-translational modifications (PTMs) has been widely studied; however, the comprehensive mechanism underlying the regulation of acetylation in bacterial resistance against antibiotics is unknown. Herein, with Escherichia coli as the model, we performed quantitative analysis of the acetylated proteome of wild-type sensitive strain (WT) and ampicillin- (Re-Amp), kanamycin- (Re-Kan), and polymyxin B-resistant (Re-Pol) strains. Based on bioinformatics analysis combined with biochemical validations, we found that a common regulatory mechanism exists between the different resistant strains. Acetylation negatively regulates bacterial metabolism to maintain antibiotic resistance, but positively regulates bacterial motility. Further analyses revealed that key enzymes in various metabolic pathways were differentially acetylated. Particularly, pyruvate kinase (PykF), a key glycolytic enzyme regulating bacterial metabolism, and its acetylated form were highly expressed in the three resistant types and were identified as reversibly acetylated by the deacetylase CobB and the acetyl-transferase PatZ, and also could be acetylated by non-enzyme AcP in vitro. Further, the deacetylation of Lys413 of PykF increased the enzyme activity by changing the conformation of ATP binding site of PykF, resulting in an increase in energy production, which in turn increased the sensitivity of drug-resistant strains to antibiotics. This study provides novel insights for understanding bacterial resistance and lays the foundation for future research on regulation of acetylation in antibiotic-resistant strains. ImportanceThe misuse of antibiotics has resulted in an emergence of a large number of antibiotic-resistant strains, which seriously threaten human health. Bacterial metabolism is tightly controlled by protein post-translational modifications, especially acetylation. However, the comprehensive mechanism underlying regulation of acetylation in bacterial resistance remains unexplored. Here, acetylation was found to positively regulate bacterial motility and negatively regulate energy metabolism, which was common in all the different antibiotic-resistant strains. Moreover, the acetylation and deacetylation process of PykF was uncovered, and deacetylation of the Lys 413 of PykF was found to contribute to bacterial sensitivity to antibiotics. This study provides a new direction for research on development of bacterial resistance through post-translational modifications and provides a theoretical basis for the development of antibacterial drugs.

microbiology↗

bioRxiv2022

Editing the CsDMR6 Gene in Citrus Results in Resistance to the Bacterial Disease Citrus Canker

Citrus is one of the most important fruit crops in the world. Citrus production worldwide faces challenges from devastating bacterial diseases, including citrus canker caused by Xanthomonas citri ssp. citri (Xcc). Improving citrus resistance to citrus canker and other major bacterial diseases has been a top priority in citrus biotechnology. Disabling disease susceptibility genes has emerged as a novel, promising approach to engineering disease resistance. The bottleneck for applying such an approach has been the identification of proper disease susceptibility-related genes in citrus. Here we show the first successful case of editing the CsDMR6 gene in citrus and obtaining strong resistance to citrus canker in six mutants in two citrus cultivars, Duncan grapefruit and Carrizo citrange. Multiple types of deletions and insertions were induced in CsDMR6, resulting in frameshift of its coding region and presumably loss of gene function. The mutation frequency in most of the mutants reached 71.8% to 98.9%. The mutants showed 71.2% to 99.8% reduction in citrus canker lesion and greater than 99.7% or 2.45 to 4.95 Log10 unit reduction in Xcc bacterial cell population. Mutants also accumulated more salicylic acid and expressed much higher levels of the NPR1 gene than the wildtype with or without Xcc inoculation, which suggests potential resistance to other diseases in these mutants. The guide RNAs for targeting CsDMR6 were selected from highly conserved regions and have 100% nucleotide identity with DMR6 homologs in important citrus species; these guide RNAs are expected to work in other important citrus species and cultivars.

plant biology↗

bioRxiv2022

A chromosome-level phased Citrus sinensis genome facilitates understanding Huanglongbing tolerance mechanisms at the allelic level in an irradiation induced mutant

Sweet orange (SWO) originated from introgressive hybridization of pummelo and mandarin resulting in a highly heterozygous genome. Here, we assembled a chromosome-level phased Valencia SWO (DVS) genome with [~]98.5% completeness, high accuracy (QV=50.6), and the highest annotation BUSCO completeness (99.2%) thus far in citrus. DVS harbors a high level of allelic variances and enables study of allelic somatic structural mutations and corresponding allelic expression alteration in two SWO mutants, one with high Huanglongbing tolerance (T19) and one more sensitive (T78). In T78, a large deletion on the pummelo-origin chr8 causes regional allelic expression absence. In T19, seven upregulated genes are located at one terminal of a translocated segment, including three genes related to heat shock protein (HSP) regulation. Furthermore, 68 of 133 HSPs are significantly upregulated in T19, which may be related to its enhanced HLB tolerance by preventing phloem necrosis. The DVS will advance allelic level studies in citrus.

plant biology↗

bioRxiv2022

Spatial and molecular anatomy of germ layers in the gastrulating primate embryo

During mammalian embryogenesis, spatial regulation of gene expression and cell signaling are functionally coupled with lineage specification, patterning of tissue progenitors and germ layer morphogenesis. While the mouse model has been instrumental for our understanding of mammalian development, comparatively little is known about human and non-human primate gastrulation due to the restriction of both technical and ethical issues. Here, we present a morphological and molecular survey of spatiotemporal dynamics of cell types populating the non-human primate embryos during gastrulation. We performed serial sections of Cynomolgus monkeys (Macaca fascicularis) gastrulating embryos at 1-day temporal resolution from E17 to E21, and reconstructed three-dimensional digital models based on high-resolution anatomical atlas that revealed the dynamic changes in the geography of the mesoderm and primitive streaks. Spatial transcriptomics identified unique gene profiles that correspond to distinct germ layers and cross-species spatiotemporal transcriptome analysis revealed a developmental coordinate of germ layer segregation between mouse and primate. Furthermore, we identified species-specific transcription programs during gastrulation. These results offer important insights into evolutionarily conserved and divergent processes during mammalian gastrulation. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=196 SRC="FIGDIR/small/474719v2_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@1058f45org.highwire.dtl.DTLVardef@105cborg.highwire.dtl.DTLVardef@12362d7org.highwire.dtl.DTLVardef@2e2346_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightO_LIA high-resolution anatomical atlas of Cynomolgus gastrulation embryos C_LIO_LICreated a three-dimensional digital template from serial sections of five developmental stages C_LIO_LIA two-dimensional spatiotemporal transcriptome of the germ layers of gastrulating embryos C_LIO_LICross-species comparison infers conservation of functional attributes of regulome and signaling activity in germ layer formation C_LI

developmental biology↗

bioRxiv2022

High-Throughput Screening for Myelination Promoting Compounds Using Human Stem Cell-derived Oligodendrocyte Progenitor Cells Identifies Novel Targets

Promoting myelination capacity of endogenous oligodendrocyte precursor cells (OPCs) is a promising therapeutic approach for central nervous system demyelinating disorders such as Multiple Sclerosis (MS). To aid in the discovery of myelination promoting compounds, we generated an advanced, genome engineered, human pluripotent stem cell (hPSC) line that consist of three reporters (identification-and-purification tag, GFP, and secreted NanoLuc) driven by the endogenous PDGFR, PLP1 and MBP genes, respectively. Based upon this line, we established a high-throughput drug screening platform and performed a small molecule screen with 2500 bioactive molecules. In addition to a number of previously known pathways, our screening effort identified new pathways whose inhibition enhance oligodendrocyte maturation and myelination. Although further genetic and molecular validation is required, the identified inhibitors could potentially be repurposed to develop remyelination therapy for MS and other demyelinating disorders.

neuroscience↗

bioRxiv2021

Metformin modulates microbiota-derived inosine and ameliorates methamphetamine-induced anxiety and depression-like withdrawal symptoms in mice

ObjectiveMetformin exhibits therapeutic potential in behavioural deficits induced by methamphetamine (METH) in rats. Emerging studies suggest gut microbiota may impact psychiatric symptoms, but there is no direct evidence supporting metformins participation in the pathophysiology of withdrawal symptoms via modulation of gut microbiota. MehodsIn order to define the functional contributions by gut microbiota and metformin to the behavioural deficits during METH withdrawal, we utilized a combination of fecal microbiota transplantation (FMT), high-throughput sequencing, and untargeted metabolomics technologies. ResultsFirst, METH addicts exhibited higher diversity and distinct microbial structures compared to heathy controls. In particular, the relative abundance of Rikenellaceae was positively correlated with the severity of anxiety and depression. Second, both human-to-mouse and mouse-to-mouse FMTs confirmed that METH-altered-microbiota transplantation is sufficient to promote anxiety and depression-like behaviours in recipient germ-free mice, and these behavioural disturbances could be ameliorated by metformin. In-depth analysis revealed that METH significantly altered the bacterial composition and structure as well as relative abundance of several bacterial taxa and metabolites, including Rikenellaceae and inosine, respectively, whereas add-on metformin could remodel these alterations. Finally, the inosine complementation successfully restored METH-induced anxiety and depression-like behaviours in mice. DiscussionThis study demonstrates that METH withdrawal-induced anxiety and depression-like behaviours are convertible and transmissible via gut microbiota in a mouse model. The therapeutic effects of metformin on psychiatric manifestations are associated with microbiota-derived metabolites, highlighting the role of the gut microbiota in substance use disorders and the pathophysiology of withdrawal symptoms. Study HighlightsO_ST_ABSWhat is known?C_ST_ABSO_LIThere are no targeted therapies for substance withdrawal syndrome, but there is considerable evidence that withdrawal-associated psychiatric manifestations contribute to the poor adherence to rehabilitation treatment as well as the relapse rates. C_LIO_LIMetformin has shown its therapeutic potential against METH-induced neurobehavioural changes and neurodegeneration in rats through CREB/BDNF and Akt/GSK3 signaling pathways in the anxiety-related brain nuclei. C_LI What is new here?O_LIMETH withdrawal-induced anxiety and depression-like behaviours are convertible and transmissible via gut microbiota in a mouse model. C_LIO_LIThe therapeutic effects of metformin on psychiatric manifestations are associated with microbiota derived metabolites. C_LIO_LIInosine complementation could restore METH withdrawal-induced anxiety and depression-like behaviours. C_LI

animal behavior and cognition↗

bioRxiv2021

Critical contribution of 3' non-seed base pairing to the in vivo function of the evolutionarily conserved let-7a microRNA

Base-pairing of the seed region (g2-g8) is essential for microRNA targeting, however, the in vivo function of the 3 non-seed region (g9-g22) are less well understood. Here we report the first systematic investigation of the in vivo roles of 3 non-seed nucleotides in microRNA let-7a, whose entire g9-g22 region is conserved among bilaterians. We found that the 3 non-seed sequence functionally distinguishes let-7a from its family paralogs. The complete pairing of g11-g16 is essential for let-7a to fully repress multiple key targets, including evolutionarily conserved lin-41, daf-12 and hbl-1. Nucleotides at g17-g22 are less critical but may compensate for mismatches in the g11-g16 region. Interestingly, the 3 non-seed pairing of let-7a can be critically required with certain minimal complementarity for sites with perfect seed pairing. These results provide evidence that the specific configurations of both seed and 3 non-seed base-pairing can critically influence microRNA-mediated gene regulation in vivo.

molecular biology↗

bioRxiv2021

Individual structural MRI abnormality indexes are associated with molecular,histological and cognitive indicators for frontal glioma patients

Although every glioma patient varies in tumor size, location, histological grade and molecular biomarkers, structural abnormalities are commonly conducted in a group-level, leading to the miss of individual structural atrophy. In this study, we introduced an individual-level structural abnormality detection method for glioma patients and proposed several novel abnormality indexes to depict the individual atrophy pattern. Forty-five glioma patients in frontal lobe and fifty-two age-matched healthy controls participated in the study. All patients underwent neurocognitive test and molecular examinations, including 1p/19q co-deletion, isocitrate dehydrogenase (IDH) mutation, telomerase reverse transcriptase (TERT) promoter mutation and O6-methylguanine-DNA methyltransferase (MGMT) promotor methylation. Individual structural abnormality maps for every glioma patient were calculated from the preoperative T1 images, and the individual abnormality index were further computed and explored the associations with clinical indicators. The results manifested that: 1. Every glioma patient show unique atrophy pattern; 2. Glioma patients also share consistent atrophy regions; 3. The atrophy pattern is influenced by some molecular biomarkers. Our study provides an effective way to access the individual structural abnormalities in glioma patients, and displays great potentials in individualized precision medicine for glioma patients.

neuroscience↗

bioRxiv2021

Cas9-cleavage sequences in minimal plasmids enhance non-viral genome targeting of CARs in primary human T cells

T cell genome editing holds great promise to advance a range of immunotherapies but is encumbered by the dependence on difficult-to-produce and expensive viral vectors. Here we have designed small double-stranded plasmid DNA modified to mediate high-efficiency homologous recombination. The resulting chimeric antigen receptor (CAR)-T cells display a similar phenotype, transcriptional profile and in vivo potency as CAR-T cells generated using adeno-associated viral (AAV) vector. This method should simplify and accelerate the use of precision engineering to produce edited T cells for research and clinical purposes.

bioengineering↗

bioRxiv2020

Soil microbial community responses to short-term nitrogen addition in Chinas Horqin Sandy Land

Anthropogenic nitrogen (N) addition has increased soil nutrient availability, thereby affecting ecosystem processes and functions in N-limited ecosystems. Long-term N addition decreases plant biodiversity, but the effects of short-term N addition on soil microbial community is poorly understood. The present study examined the impacts of short-term N addition (NH4NO3) on these factors in a sandy grassland and semi-fixed sandy land in the Horqin Sandy Land. We measured the responses of soil microbial biomass C and N; on soil {beta}-1,4-glucosidase (BG) and {beta}-1,4-N-acetylglucosaminidase (NAG) activity; and soil microflora characteristics to N additions gradient with 0 (control), 5 (N5), 10 (N10), and 15 (N15) g N m-2 yr-1. The soil microbial biomass indices, NAG activity, and soil microflora characteristics did not differ significantly among the N levels, and there was no difference at the two sites. The competition for N between plants and soil microbes was not eliminated by short-term N addition due to the low soil nutrient and moisture contents, and the relationships among the original soil microbes did not change. However, N addition increased BG activity in the N5 and N10 additions in the sandy grassland, and in the N5, N10, and N15 additions in the semi-fixed sandy land. This may be due to increased accumulation and fixation of plant litter into soils in response to N addition, leading to increased microbial demand for a C source and increased soil BG activity. Future research should explore the relationships between soil microbial community and N addition at the two sites.

ecology↗

bioRxiv2020

Up-Regulation of αCaMKII Impairs Cued Fear Extinction and NMDAR-Dependent LTD in the Lateral Amygdala

Impaired fear extinction is one of the hallmark symptoms of post-traumatic stress disorder (PTSD). The roles of CaMKII have been not extensively studied in fear extinction and LTD. Here, we found PTSD susceptible mice exhibited significant up-regulation of CaMKII in the lateral amygdala (LA). Consistently, increasing CaMKII in LA profoundly not only caused PTSD-like symptoms such as impaired fear extinction and anxiety-like behaviors, but also attenuated NMDAR-dependent LTD at thalamo-LA synapses, reduced GluA1-Ser845/Ser831 dephosphorylation and AMPAR internalization. Suppressing the elevated CaMKII to normal level could completely reverse both PTSD-like symptoms and the impairments in LTD, GluA1-Ser845/Ser831 dephosphorylation and AMPAR internalization. Intriguingly, deficits in AMPAR internalization and GluA1-Ser845/Ser831 dephosphorylation were detected not only after impaired fear extinction, but also after attenuated LTD Our results demonstrate for the first time GluA1-Ser845/Ser831 dephosphorylation and AMPAR internalization are molecular links between LTD and fear extinction, and suggest CaMKII may be a potential molecular determinant of PTSD.

neuroscience↗

bioRxiv2020

A P2rx7 passenger mutation affects the vitality and function of immune cells in P2X4ko and other transgenic mice

Among laboratory mouse strains many genes are differentially expressed in the same cell population. As consequence, gene targeting in 129-derived embryonic stem cells (ESCs) and backcrossing the modified mice onto the C57BL/6 (B6) background can introduce passenger mutations in the close proximity of the targeted gene. Here, we demonstrate that several 129-originating transgenic mice in which P2rx7-neighboring genes were targeted carry a P2rx7 passenger mutation that affects the vitality and function of T cells. By the example of P2rx4tm1Rass we demonstrate that CD4+ and CD8+ T cells derived from these mice express higher levels of P2X7 when compared to corresponding cell populations in B6-WT mice. The increased T cell sensitivity towards the P2X7 activators adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide (NAD+) rendered these cells more vulnerable towards NAD-induced cell death (NICD) compared to their B6-WT counterparts. The enhanced NICD sensitivity significantly affected the outcome of functional assays e.g. cytokine production and cell migration. For P2rx4tm1Rass, we demonstrate that the expression of P2X7 is diminished in several innate immune cell populations, possibly as a side effect of P2rx4 targeting, and independent of the P2rx7 passenger mutation. These results need to be considered when working with P2rx4tm1Rass mice or other 129-based transgenic strains that target P2rx7 neighboring genes and might have implications for other mouse models.

immunology↗

bioRxiv2020

CHMP2B regulates TDP-43 phosphorylation and proteotoxicity via modulating CK1 turnover independent of the autophagy-lysosomal pathway

Protein inclusions containing phosphorylated TDP-43 are a shared pathology in several neurodegenerative diseases including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, most ALS/FTD patients do not have a mutation in TDP-43 or the enzymes directly regulating its phosphorylation. It is intriguing how TDP-43 becomes hyperphosphorylated in each disease condition. In a genetic screen for novel TDP-43 modifiers, we found that knockdown (KD) of CHMP2B, a key component of the endosomal sorting complex required for transport (ESCRT) machinery, suppressed TDP-43-mediated neurodegeneration in Drosophila. Further investigation using mammalian cells indicated that CHMP2B KD decreased whereas its overexpression (OE) increased TDP-43 phosphorylation levels. Moreover, a known FTD-causing mutation CHMP2Bintron5 promoted hyperphosphorylation, insolubility and cytoplasmic accumulation of TDP-43. Interestingly, CHMP2B did not manifest these effects by its well-known function in the autophagy-lysosomal pathway. Instead, the kinase CK1 tightly regulated TDP-43 phosphorylation level in cells, and CHMP2B OE or CHMP2BIntron5 significantly decreased ubiquitination and the turnover of CK1 via the ubiquitin-proteasome (UPS) pathway. Finally, we showed that CHMP2B protein levels increased in the cerebral cortices of aged mice, which might underlie the age-associated TDP-43 pathology and disease onset. Together, our findings reveal a molecular link between the two ALS/FTD-pathogenic proteins CHMP2B and TDP-43, and provide an autophagy-independent mechanism for CHMP2B in pathogenesis. SIGNIFICANCE STATEMENTTDP-43 and CHMP2B are both ALS/FTD-associated proteins. Protein aggregations containing phosphorylated TDP-43 are a pathological hallmark of ALS/FTD; however, it is unclear how increased phosphorylation of TDP-43 occurs in diseases. The pathogenesis of CHMP2B has mainly been considered as a consequence of autophagy-lysosomal dysfunction. Here, we reveal that increase of CHMP2B levels (which occurs in aged mouse brains) or expression of the disease-causing mutation CHMP2BIntron5 promotes TDP-43 hyperphosphorylation, insolubility and cytoplasmic mislocalization. This effect is independent of the autophagy-lysosomal pathway but rather relies on the proteasome-mediated turnover of the kinase CK1 that phosphorylates TDP-43. Together, we provide a new molecular mechanism of CHMP2B pathogenesis by linking it to TDP-43 pathology via CK1.

neuroscience↗

bioRxiv2020

Structural basis for the inhibition of COVID-19 virus main protease by carmofur, an antineoplastic drug

The antineoplastic drug Carmofur was shown to inhibit SARS-CoV-2 main protease (Mpro). Here the X-ray crystal structure of Mpro in complex with Carmofur reveals that the carbonyl reactive group of Carmofur is covalently bound to catalytic Cys145, whereas its fatty acid tail occupies the hydrophobic S2 subsite. Carmofur inhibits viral replication in cells (EC50 = 24.30 M) and it is a promising lead compound to develop new antiviral treatment for COVID-19.

biochemistry↗

bioRxiv2020

Visual function restoration in genetically blind mice via endogenous cellular reprogramming

In this study, we developed an in-situ cellular reprogramming strategy for potent restoration of vision in advanced/end-stage retinitis pigmentosa (RP). Via repressing PTB, an RNA binding protein critical for converting non-neuronal cells to the neuronal lineage, we successfully reprogramed Muller glia to a retinal neuronal fate, and then to cones. We demonstrated that this cellular reprogramming approach was able to rescue retinal photoreceptor degeneration and restore visual functions in two RP mouse models with total blindness, suggesting a novel universal strategy for treating end-stage degenerative diseases.

cell biology↗

bioRxiv2020

Atlas of ACE2 gene expression in mammals reveals novel insights in transmission of SARS-Cov-2

BackgroundCOVID-19 has become a worldwide pandemic. It is caused by a novel coronavirus named SARS-CoV-2 with elusive origin. SARS-CoV-2 infects mammalian cells by binding to ACE2, a transmembrane protein. Therefore, the conservation of ACE2 and its expression pattern across mammalian species, which are yet to be comprehensively investigated, may provide valuable insights into tracing potential hosts of SARS-CoV-2. MethodsWe analyzed gene conservation of ACE2 across mammals and collected more than 140 transcriptome datasets from human and common mammalian species, including presumed hosts of SARS-CoV-2 and other animals in close contact with humans. In order to enable comparisons across species and tissues, we used a unified pipeline to quantify and normalize ACE2 expression levels. ResultsWe first found high conservation of ACE2 genes among common mammals at both DNA and peptide levels, suggesting that a broad range of mammalian species can potentially be the hosts of SARS-CoV-2. Next, we showed that high level of ACE2 expression in certain human tissues is consistent with clinical symptoms of COVID-19 patients. Furthermore, we observed that ACE2 expressed in a species-specific manner in the mammals examined. Notably, high expression in skin and eyes in cat and dog suggested that these animals may play roles in transmitting SARS-CoV-2 to humans. ConclusionsThrough building the first atlas of ACE2 expression in pets and livestock, we identified species and tissues susceptible to SARS-CoV-2 infection, yielding novel insights into the viral transmission.

genomics↗