Biology subjects

Chen, D.

Publications and source records attributed to Chen, D..

At least 271 records · Page 15Linked to original sources

bioRxiv2021

Transcriptomic Profiling Reveals Cancer-Associated Fibroblasts as Potential Targets for the Prognosis and Treatment of Cervical Squamous Cell Carcinoma

Effective treatment of advanced invasive cervical cancer remains challenging nowadays. Herein, single-nucleus RNA sequencing (snRNA-seq) and SpaTial Enhanced REsolution Omics-sequencing (Stereo-seq) technology are used to investigate the immunological microenvironment of cervical squamous cell carcinoma (CSCC), a major type of cervical cancers. The expression levels of most immune checkpoint genes in tumor and inflammation areas of CSCC were not significantly higher than those in the non-cancer samples except for LGALS9 and IDO1. Stronger signals of CD56+ NK cells and immature dendritic cells are found in the hypermetabolic tumor areas, while more eosinophils, immature B cells, and Treg cells are found in the hypometabolic tumor areas. Moreover, a cluster of cancer-associated fibroblasts (CAFs) are identified around some tumors, which highly expressed ACTA2, POSTN, ITGB4, and FAP. The CAFs might support the growth and metastasis of tumors by inhibiting lymphocyte infiltration and remodeling the tumor extracellular matrix. Furthermore, CAFs are associated with poorer survival probability in CSCC patients and might be present in a small fraction ([~]20%) of advanced cancer patients. Collectively, these findings might enhance understanding of the CSCC immunological microenvironment and shed some light on the treatment of advanced CSCC.

cancer biology↗

bioRxiv2021

Scellseg: a style-aware cell instance segmentation tool with pre-training and contrastive fine-tuning

Deep learning-based cell segmentation is increasingly utilized in cell biology and molecular pathology, due to massive accumulation of diverse large-scale datasets and excellent progress in cell representation. However, the development of specialized algorithms has long been hampered by a paucity of annotated training data, whereas the performance of generalist algorithm was limited without experiment-specific calibration. Here, we present a deep learning-based tool called Scellseg consisted of novel pre-trained network architecture and contrastive fine-tuning strategy. In comparison to four commonly used algorithms, Scellseg outperformed others in average precision and Aggregated Jaccard Index on three disparate datasets. Interestingly, we found that eight images are sufficient for model tuning to achieve satisfied performance based on a shot data scale experiment. We also developed a graphical user interface integrated with functions of annotation, fine-tuning and inference, that allows biologists to easily specialize their self-adaptive segmentation model for analyzing images at the single-cell level.

bioinformatics↗

bioRxiv2021

Molecular mechanisms governing circulating immune cell heterogeneity across different species revealed by single cell sequencing

BackgroundImmune cells play important roles in mediating immune response and host defense against invading pathogens. However, insights into the molecular mechanisms governing circulating immune cell diversity among multiple species are limited. MethodsIn this study, we compared the single-cell transcriptomes of 77{square}957 immune cells from 12 species using single-cell RNA-sequencing (scRNA-seq). Distinct molecular profiles were characterized for different immune cell types, including T cells, B cells, natural killer cells, monocytes, and dendritic cells. ResultsResults revealed the heterogeneity and compositions of circulating immune cells among 12 different species. Additionally, we explored the conserved and divergent cellular crosstalk and genetic regulatory networks among vertebrate immune cells. Notably, the ligand and receptor pair VIM-CD44 was highly conserved among the immune cells. ConclusionsThis study is the first to provide a comprehensive analysis of the cross-species single-cell atlas for peripheral blood mononuclear cells (PBMCs). This research should advance our understanding of the cellular taxonomy and fundamental functions of PBMCs, with important implications in evolutionary biology, developmental biology, and immune system disorders.

cell biology↗

bioRxiv2021

Connectome-wide association analysis identified significant brain functional alteration in adults with attention-deficit/hyperactivity disorder

Adults with attention-deficit/hyperactivity disorder (ADHD), as an extreme-phenotype of ADHD, is still facing problems of inconsistency and undeciphered mechanisms for its neuropathology. To address this matter, our present study performed connecotome-wide voxel-based analyses with the resting-state fMRI data of 84 adults with ADHD and 89 healthy controls. We found that functional connectivity patterns of the left precuneus and the left middle temporal significantly altered in ADHD populations serving as potential neural biomarkers to distinguish ADHD with healthy controls, with subsequent seed-based analysis revealing the dysfunction of functional connections both intra- and inter-default mode and attention networks, among which middle temporal gyrus plays the key role of bridge linking the default mode and attention networks. After cognitive behavioral therapy, two of these ADHD-altered functional connections ameliorated accompanied with improvement of ADHD core symptoms. Additionally, imaging genetic analyses also revealed close relationships between the observed brain functional alterations and ADHD-risk genes. Taken together, our findings suggested the interference of default mode on attention networks in adults with ADHD, which would be severing as a potential biomarker for both ADHD pathogenesis and treatment effects.

neuroscience↗

bioRxiv2021

Multi-omics Analyses Provides Insight into the Biosynthesis Pathways of Fucoxanthin in Isochrysis galbana

Isochrysis galbana is considered an ideal bait for functional foods and nutraceuticals in humans because of its high fucoxanthin (Fx) content. However, multi-omics analysis of the regulation networks for Fx biosynthesis in I. galbana has not been reported. In this study, we report a high-quality genome sequence of I. galbana LG007, which has a 92.73 Mb genome size, with a contig N50 of 6.99 Mb and 14,900 protein-coding genes. Phylogenomic inferences confirmed the monophyly of Haptophyta, with I. galbana sister to Emiliania huxleyi and Chrysochromulina tobinii. Evolutionary analysis revealed an estimated divergence time between I. galbana and E. huxleyi of ~ 133 million years ago (Mya). Gene family analysis indicated that lipid metabolism-related genes exhibited significant expansion, including IgPLMT, IgOAR1 and {Delta}-4 desaturase. Metabolome analysis showed that the content of carotenoid in I. galbana cultured under green light for 7 days was higher than that of white light, and {beta}-carotene was the main carotenoids, accounting for 79.09% of the total carotenoids. Comprehensive analysis of multi-omics analysis revealed that {beta}-carotene, antheraxanthin, zeaxanthin, and Fx content was increased by green light induction, which was significantly correlated with the expression of IgMYB98, IgZDS, IgPDS, IgLHCX2, IgZEP, IgLCYb, and IgNSY. These findings contribute to understanding Fx biosynthesis and its regulation, providing a valuable reference for food and pharmaceutical applications.

bioinformatics↗

bioRxiv2021

Landscape, complexity and regulation of a filamentous fungal transcriptome

Alternative splicing (AS) and alternative polyadenylation (APA) of pre-mRNAs contribute greatly to transcriptome complexity and gene expression regulation in higher eukaryotes. Their biological impact in filamentous fungi, however, has been poorly studied. Here we combine PacBio Isoform Sequencing and strand-specific RNA-Seq of multiple tissues together with mutant characterization to reveal the landscape, complexity and regulation of AS and APA in the filamentous plant pathogenic fungus Fusarium graminearum. We updated the reference genome and generated a comprehensive annotation comprising 51,617 transcript isoforms from 17,189 genes. Majority of the transcripts represent novel isoforms, including 2,998 undiscovered protein-coding genes. In total, 42.7% of multi-exonic genes and 64.8% of genes have AS and APA isoforms, respectively, suggesting AS and APA increase previously unrecognized transcriptome complexity in fungi. Nonsense-mediated mRNA decay factor FgUPF1 may not degrade AS transcripts with premature-stop codons but regulate ribosome biogenesis. Distal polyadenylation sites have a strong signal but proximal polyadenylation isoforms are high expressed. The core 3-end processing factors FgRNA15, FgHRP1, and FgFIP1 play important roles in promoting proximal polyadenylation site usage and also intron splicing. Genome-wide increase in the abundance of transcripts with retained introns and long 3-UTRs and downregulation of the spliceosomal and 3-end processing factors are found in older tissues and quiescent conidia, indicating that intron retention and 3-UTR lengthening may be a transcriptional signature of aging and dormancy in fungi. Overall, our study generates a comprehensive full-length transcript annotation for F. graminearum and provides new insights into the complexity and regulation of transcriptome in filamentous fungi.

genomics↗

bioRxiv2021

Polycystin-2 is upregulated in fibrotic kidneys and inhibition of plycystin-2 by triptolide attenuates renal fibrosis

Mutations in PKD1 (encoding polycystin-1) or PKD2 (encoding polycystin-2) gene cause autosomal dominant polycystic kidney disease (ADPKD), however high levels of polycystins are detected in renal tissues of ADPKD patients. Animal studies showed that loss and gain of function of polycystins are both pathogenic and can induce cystic phenotype in the kidney, which are associated with enhanced renal fibrosis. Recent studies showed that increased expression of polycystins contributes to organ fibrosis. However, the role of polycystins in renal tubulointerstitial fibrosis remains unclear. In this study, we demonstrated that polycystin-1 or polycystin-2 was highly expressed in the kidney of two different fibrotic mouse models and positively correlated with expression of collagen-I. Pharmaceutical inhibition of polycystin-2 with triptolide or genetic knockout of polycystin-2 reduced the expression of epithelial-mesenchymal transition (EMT) markers and deposition of extracellular matrix proteins in fibrotic kidneys. Similarly, conditional knockout of Pkd1 gene also attenuated renal fibrosis in mouse models. Thus, we further hypothesized that inhibition of polycystins delays cyst growth by mitigating renal fibrosis. Here, we showed that polycystin-1 or polycystin-2 was up-regulated in Pkd2 or Pkd1 mice respectively and tightly correlated with the growth of renal cysts and fibrosis development. Genetic deletion of both polycystin-1 and polycystin-2 retarded cyst growth in Pkd1 or Pkd2 mice. Finally, we deleted pkd1 gene in a fibrosis triggered adult ADPKD mouse model at different time point before or after the fibrotic injury. We showed that early and long-term inactivation of Pkd1 delayed fibrosis triggered renal cyst growth in adult Pkd1 mice as compared with mice with late and short-term inactivation of Pkd1 gene. We conclude that tubular obstruction induced polycystin up-regulation is pro-fibrotic and accelerates cyst growth through enhancing renal interstitial fibrosis in ADPKD mice. Our study indicates that ADPKD is caused by both loss and gain function of polycystins. Reduction of the aberrant upregulation of polycystins in cystic kidneys is a therapeutic option for ADPKD patients. Research highlightsO_LIPolycystin1 and polycystin-2 are up-regulated in fibrotic kidneys C_LIO_LIInhibition or deletion of polycystins inhibits EMT and attenuates renal tubulointerstitial fibrosis C_LIO_LIUpregulation of polycystin1 or polycystin-2 is positively correlated with fibrosis progression and renal cyst growth in ADPKD mice C_LIO_LIDouble knockout of Pkd1 and Pkd2 gene inhibits renal cyst growth in ADPKD mice C_LIO_LILong-term deletion of Pkd1 gene delayed fibrosis triggered renal cyst growth in ADPKD mice C_LI

pathology↗

bioRxiv2021

Directional selection at gene expression level contributes to the speciation of Asian rice cultivars

Differences in expression levels play important roles in phenotypic variation across species, especially those closely related species with limited genomic differences. Therefore, studying gene evolution at expression level is important for illustrating phenotypic differentiation between species, such as the two Asian rice cultivars, Oryza sativa L. ssp. indica and Oryza sativa L. ssp. japonica. In this study, we evaluated the gene expression variation at inter-subspecies and intra-subspecies level using transcriptome data from seedlings of three indica and japonica rice and defined four groups of genes under different natural selections. We found a substantial of genes (about 79%) that are under stabilizing selection at the expression level in both subspecies, while about 16% of genes are under directional selection. Genes under directional selection have higher expression level and lower expression variation than those under stabilizing selection, which suggest a potential explanation to subspecies adaptation to different environments and interspecific phenotypic differences. Subsequent functional enrichment analysis of genes under directional selection shows that indica rice have experienced the adaptation to environmental stresses, and also show differences in biosynthesis and metabolism pathways. Our study provide an avenue of investigating indica-japonica differentiation through gene expression variation, which may guide to rice breeding and yield improvement.

plant biology↗

bioRxiv2021

H3K9me1/2 methylation limits the lifespan of C. elegans

Histone methylation plays crucial roles in the development, gene regulation and maintenance of stem cell pluripotency in mammals. Recent work shows that histone methylation is associated with aging, yet the underlying mechanism remains unclear. In this work, we identified a class of histone 3 lysine 9 mono-/dimethyltransferase genes (met-2, set-6, set-19, set-20, set-21, set-32 and set-33), mutations in which induce synergistic lifespan extension in the long-lived DAF-2 (IGF-1 receptor) mutant in C. elegans. These histone methyltransferase plus daf-2 double mutants not only exhibited an average lifespan nearly three times that of wild-type animals and a maximal lifespan of approximately 100 days, but also significantly increased resistance to oxidative and heat stress. Synergistic lifespan extension depends on the transcription factor DAF-16 (FOXO). mRNA-seq experiments revealed that the mRNA levels of class I DAF-16 target genes, which are activated by DAF-16, were further elevated in the double mutants. Among these genes, F35E8.7, nhr-62, sod-3, asm-2 and Y39G8B.7 are required for the lifespan extension of the daf-2;set-21 double mutant. In addition, treating daf-2 animals with the H3K9me1/2 methyltransferase G9a inhibitor also extends lifespan and increases stress resistance. Therefore, investigation of DAF-2 and H3K9me1/2 methyltransferase deficiency-mediated synergistic longevity will contribute to a better understanding of the molecular mechanisms of aging and therapeutic applications.

genetics↗

bioRxiv2021

Aggregation pheromone 4-vinylanisole promotes the synchrony of sexual maturation in female locusts

Reproductive synchrony generally occurs in various group-living animals; however, the underlying mechanisms remain largely unexplored. Here, we report that aggregation pheromone, 4-vinylanisole, plays a key role in promoting sexual maturation synchrony of female adults in the migratory locust, Locusta migratoria, a worldwide agricultural pest species that can form huge swarms with millions of individuals. Gregarious female locusts display significant synchrony of sexual maturation and oviposition whereas solitarious females and olfactory deficiency mutants do not. Only the presence of gregarious male adults can stimulate sexual maturation synchrony of female adults. Of the volatiles emitted abundantly by gregarious male adults, only 4-vinylanisole induces female sexual maturation synchrony, whereas this effect is abolished in mutants of 4- vinylanisole receptor. Interestingly, 4-vinylanisole mainly accelerates oocyte maturation of young females aged at middle developmental stages (3-4 days post adult eclosion). Juvenile hormone/vitellogenin pathway mediates female sexual maturation triggered by 4-vinylanisole. Our results highlight a "catch-up" strategy by which gregarious females synchronize their oocyte maturation and oviposition by time-dependent endocrinal response to 4-vinylanisole.

ecology↗

bioRxiv2021

Neural dynamics of retrieval suppression in abolishing item-specific cortical pattern of unwanted emotional memories

When reminded of an unpleasant experience, people often try to exclude the unwanted memory from awareness, a process known as retrieval suppression. Despite the importance of this form of mental control to mental health, the ability to track, in real time, individual memories as they are suppressed remains elusive. Here we used multivariate decoding on EEG data to track how suppression unfolds in time and to reveal its impact on cortical patterns related to individual memories. We presented reminders to aversive scenes and asked people to either suppress or to retrieve the scene. During suppression, mid-frontal theta power within the first 500 ms distinguished suppression from passive viewing of the reminder, indicating that suppression rapidly recruited control. During retrieval, we could discern EEG cortical patterns relating to individual memories-initially, based on theta-driven, visual perception of the reminders (0-500 ms) and later, based on alpha-driven, reinstatement of the aversive scene (500-3000 ms). Critically, suppressing retrieval weakened (during 420-600 ms) and eventually abolished item-specific cortical patterns, a robust effect that persisted until the reminder disappeared (1200-3000 ms). Actively suppressing item-specific cortical patterns, both during an early (300-680 ms) window and during sustained control, predicted later episodic forgetting. Thus, both rapid and sustained control contribute to abolishing cortical patterns of individual memories, limiting awareness, and precipitating later forgetting. These findings reveal how suppression of individual memories from awareness unfolds in time, presenting a precise chronometry of this process.

neuroscience↗

bioRxiv2021

SomaticSiMu: a mutational signature simulator

SummarySomaticSiMu is an in silico simulator of single and double base substitutions, and single base insertions and deletions in an input genomic sequence to mimic mutational signatures. SomaticSiMu outputs simulated DNA sequences and mutational catalogues with imposed mutational signatures. The tool is the first mutational signature simulator featuring a graphical user interface, control of mutation rates, and built-in visualization tools of the simulated mutations. Simulated datasets are useful as a ground truth to test the accuracy and sensitivity of DNA sequence classification tools and mutational signature extraction tools under different experimental scenarios. The reliability of SomaticSiMu was affirmed by 1) supervised machine learning classification of simulated sequences with different mutation types and burdens, and 2) mutational signature extraction from simulated mutational catalogs. Availability and ImplementationSomaticSiMu is written in Python 3.8.3. The open-source code, documentation, and tutorials are available at https://github.com/HillLab/SomaticSiMu under the terms of the Creative Commons Attribution 4.0 International License. Contactkhill22@uwo.ca Supplementary informationSupplementary data are available at Bioinformatics online.

bioinformatics↗

bioRxiv2021

Midkine noncanonically suppresses AMPK activation through disrupting the LKB1-STRAD-Mo25 complex

Midkine (MDK), an extracellular growth factor, regulates signal transduction and cancer progression by interacting with receptors, and it can be internalized into the cytoplasm by endocytosis. However, its intracellular function and signaling regulation remain unclear. Here, we show that intracellular MDK interacts with LKB1 and STRAD to disrupt the LKB1-STRAD-Mo25 complex. Consequently, MDK decreases the activity of LKB1 to dampen both the basal and stress-induced activation of AMPK by glucose starvation or treatment of 2-DG. We also found that MDK accelerates cancer cell proliferation by inhibiting the activation of the LKB1-AMPK axis. In human cancers, compared to other well-known growth factors, MDK expression is most significantly upregulated in cancers, especially in liver, kidney and breast cancers, correlating with clinical outcomes and inversely correlating with PRKAA1 (encoding AMPK1) expression and phosphorylated AMPK levels. Our study elucidates an inhibitory mechanism for AMPK activation, which is mediated by the intracellular MDK through disrupting the LKB1-STRAD-Mo25 complex.

cancer biology↗

bioRxiv2021

Mechanical stimulation promotes enthesis injury repair by mobilizing Prx1+ cells via ciliary TGF-β signaling

Proper mechanical stimulation can improve rotator cuff enthsis injury repair. However, the underlying mechanism of mechanical stimulation promoting injury repair is still unknown. In this study, we found that Prx1+ cell was essential for murine rotator cuff enthesis development identified by single-cell RNA sequence and involved in the injury repair. Proper mechanical stimulation could promote the migration of Prx1+ cells to enhance enthesis injury repair. Meantime, TGF-{beta} signaling and primary cilia played an essential role in mediating mechanical stimulation signaling transmission. Proper mechanical stimulation enhanced the release of active TGF-{beta}1 to promote migration of Prx1+ cells. Inhibition of TGF-{beta} signaling eliminated the stimulatory effect of mechanical stimulation on Prx1+ cell migration and enthesis injury repair. In addition, knockdown of Pallidin to inhibit TGF-{beta}R2 translocation to the primary cilia or deletion of IFT88 in Prx1+ cells also restrained the mechanics-induced Prx1+ cells migration. These findings suggested that mechanical stimulation could increase the release of active TGF-{beta}1 and enhance the mobilization of Prx1+ cells to promote enthesis injury repair via ciliary TGF-{beta} signaling.

cell biology↗

bioRxiv2021

Glycosaminoglycans Modulate Long-Range Mechanical Communication Between Cells in Collagen Networks

Cells can sense and respond to mechanical forces in fibrous extracellular matrices (ECM) over distances much greater than their size. This phenomenon, termed long-range force transmission, is enabled by the realignment (buckling) of collagen fibers along directions where the forces are tensile (compressive). However, whether other key structural components of the ECM, in particular glycosaminoglycans (GAGs), can affect the efficiency of cellular force transmission remains unclear. Here we developed a theoretical model of force transmission in collagen networks with interpenetrating GAGs, capturing the competition between tension-driven collagen-fiber alignment and the swelling pressure induced by GAGs. Using this model, we show that the swelling pressure provided by GAGs increases the stiffness of the collagen network by stretching the fibers in an isotropic manner. We found that the GAG-induced swelling pressure can help collagen fibers resist buckling as the cells exert contractile forces. This mechanism impedes the alignment of collagen fibers and decreases long-range cellular mechanical communication. We experimentally validated the theoretical predictions by comparing collagen fiber alignment between cellular spheroids cultured on collagen gels versus collagen-GAG co-gels. We found significantly less alignment of collagen in collagen-GAG co-gels, consistent with the prediction that GAGs can prevent collagen fiber alignment. The roles of GAGs in modulating force transmission uncovered in this work can be extended to understand pathological processes such as the formation of fibrotic scars and cancer metastasis, where cells communicate in the presence of abnormally high concentrations of GAGs. Statement of significanceGlycosaminoglycans (GAGs) are carbohydrates that are expressed ubiquitously in the human body and are among the key macromolecules that influence development, homeostasis, and pathology of native tissues. Abnormal accumulation of GAGs has been observed in metabolic disorders, solid tumors, and fibrotic tissues. Here we theoretically and experimentally show that tissue swelling caused by the highly polar nature of GAGs significantly affects the mechanical interactions between resident cells by altering the organization and alignment of the collagenous extracellular matrix. The roles of GAGs in modulating cellular force transmission revealed here can guide the design of biomaterial scaffolds in regenerative medicine and provides insights on the role of cell-cell communication in tumor progression and fibrosis.

biophysics↗

bioRxiv2021

Temporal inhibition of chromatin looping and enhancer accessibility during neuronal remodeling

During development, looping of an enhancer to a promoter is frequently observed in conjunction with temporal and tissue-specific transcriptional activation. The chromatin insulator-associated protein Shep promotes Drosophila post-mitotic neuronal remodeling by repressing transcription of master developmental regulators, such as brain tumor (brat), specifically in maturing neurons. Since insulator proteins can promote looping, we hypothesized that Shep antagonizes brat promoter interaction with an as yet unidentified enhancer. Using chromatin conformation capture and reporter assays, we identified two novel enhancer regions that increase in looping frequency with the brat promoter specifically in pupal brains after Shep depletion. The brat promoters and enhancers function independently of Shep, ruling out direct repression of these elements. Moreover, ATAC-seq in isolated neurons demonstrated that Shep restricts chromatin accessibility of a key brat enhancer as well as other enhancers genome-wide in remodeling pupal but not larval neurons. These enhancers are enriched for chromatin targets of Shep and are located at Shep-inhibited genes, suggesting direct Shep inhibition of enhancer accessibility and gene expression during neuronal remodeling. Our results provide evidence for temporal regulation of chromatin looping and enhancer accessibility during neuronal maturation.

genomics↗

bioRxiv2021

CDCP: a visualization and analyzing platform for single-cell datasets

Advances in single-cell sequencing technology provide a unique approach to characterize the heterogeneity and distinctive functional states at single-cell resolution, leading to rapid accumulation of large-scale single-cell datasets. A big challenge undertaken by research community especially bench scientists is how to simplify the way of retrieving, processing and analyzing the huge number of datasets. Towards this end, we developed Cell-omics Data Coordinate Platform (CDCP), a platform that aims to share and integrate comprehensive single-cell datasets, and to provide a network analysis toolkit for personalized analysis. CDCP contains single-cell RNA-seq and ATAC-seq datasets of 474 572 cells from 6 459 samples in species covering humans, non-human primate models and other animals. It allows querying and visualization of interested datasets and the expression profile of distinct genes in different cell clusters and cell types. Besides, this platform provides an analysis pipeline for non-bioinformatician experimental scientists to address questions not focused by the submitters of the datasets. In summary, CDCP provides a user-friendly interface for researchers to explore, visualize, analyze, download and submit published single-cell datasets and it will be a valuable resource for investigators to explore the global transcriptome profiling at single-cell level.

bioinformatics↗

bioRxiv2021

Screening of cell-virus, cell-cell, gene-gene interactions among kingdoms of life at single cell resolution

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) issued a significant and urgent threat to global health. The exact animal origin of SARS-CoV-2 remains obscure and understanding its host range is vital for preventing interspecies transmission. Previously, we have assessed the target cell profiles of SARS-CoV-2 in pets, livestock, poultry and wild animals. Herein, we expand this investigation to a wider range of animal species and viruses to provide a comprehensive source for large-scale screening of potential virus hosts. Single cell atlas for several mammalian species (alpaca, hamster, hedgehog, chinchilla etc.), as well as comparative atlas for lung, brain and peripheral blood mononuclear cells (PBMC) for various lineages of animals were constructed, from which we systemically analyzed the virus entry factors for 113 viruses over 20 species from mammalians, birds, reptiles, amphibians and invertebrates. Conserved cellular connectomes and regulomes were also identified, revealing the fundamental cell-cell and gene-gene cross-talks between these species. Overall, our study could help identify the potential host range and tissue tropism of SARS-CoV-2 and a diverse set of viruses and reveal the host-virus co-evolution footprints.

cell biology↗