Mutational signature and prognosis in adenocarcinoma of the bladder.

Adenocarcinoma of the bladder is a rare urinary bladder carcinoma with limited therapy options due to lack of molecular characterization. Here, we aimed to reveal the mutational and transcriptomic landscapes of adenocarcinoma of the bladder and assess any relationship with prognosis. Between February 2015 and June 2021, a total of 23 patients with adenocarcinoma of the bladder were enrolled. These included 16 patients with primary bladder adenocarcinomas and seven patients with urachal adenocarcinoma. Whole exome sequencing (16 patients), whole genome sequencing (16 patients), bulk RNA sequencing (RNA-seq) (19 patients), and single-cell RNA-seq (5 patients) were conducted for the specimens. Correlation analysis, survival analysis, and t-tests were also performed. Prevalent T>A substitutions were observed among somatic mutations, and major trinucleotide contexts included 5'-CTC-3' and 5'-CTG-3'. This pattern was mainly contributed by COSMIC signature 22 related to chemical carcinogen exposure (probably aristolochic acid), which has not been reported in bladder adenocarcinoma. Moreover, genes with copy number changes were also enriched in the KEGG term 'chemical carcinogenesis'. Transcriptomic analysis suggested high immune cell infiltration and luminal-like features in the majority of samples. Interestingly, a small fraction of samples with an APOBEC-derived mutational signature exhibited a higher risk of disease progression compared with samples with only a chemical carcinogen-related signature, confirming the molecular and prognostic heterogeneity of bladder adenocarcinoma. This study presents mutational and transcriptomic landscapes of bladder adenocarcinoma, and indicates that a chemical carcinogen-related mutational signature may be related to a better prognosis compared with an APOBEC signature in adenocarcinoma of the bladder. © 2024 The Pathological Society of Great Britain and Ireland.

LZP is required for hepatic triacylglycerol transportation through maintaining apolipoprotein B stability.

The conserved zona pellucida (ZP) domain is found in hundreds of extracellular proteins that are expressed in various organs and play a variety of roles as structural components, receptors and tumor suppressors. A liver-specific zona pellucida domain-containing protein (LZP), also named OIT3, has been shown to be mainly expressed in human and mouse hepatocytes; however, the physiological function of LZP in the liver remains unclear. Here, we show that Lzp deletion inhibited very low-density lipoprotein (VLDL) secretion, leading to hepatic TG accumulation and lower serum TG levels in mice. The apolipoprotein B (apoB) levels were significantly decreased in the liver, serum, and VLDL particles of LZP-deficient mice. In the presence of LZP, which is localized to the endoplasmic reticulum (ER) and Golgi apparatus, the ER-associated degradation (ERAD) of apoB was attenuated; in contrast, in the absence of LZP, apoB was ubiquitinated by AMFR, a known E3 ubiquitin ligase specific for apoB, and was subsequently degraded, leading to lower hepatic apoB levels and inhibited VLDL secretion. Interestingly, hepatic LZP levels were elevated in mice challenged with a high-fat diet and humans with simple hepatic steatosis, suggesting that LZP contributes to the physiological regulation of hepatic TG homeostasis. In general, our data establish an essential role for LZP in hepatic TG transportation and VLDL secretion by preventing the AMFR-mediated ubiquitination and degradation of apoB and therefore provide insight into the molecular function of LZP in hepatic lipid metabolism.

Exploring the impact of nonylphenol exposure on Litopenaeus vannamei at the histological and molecular levels.

Nonylphenol (NP) is one of the common pollutants in the environment that have toxic effects on aquatic animals. Nevertheless, little is known about the possible toxicity mechanism of NP on the hepatopancreas of Litopenaeus vannamei. In the present study, the detrimental effects of NP on the hepatopancreas of the L. vannamei were explored at the histological and transcriptomic levels. The findings indicated that after NP exposed for 3, 12, and 48 h, the hepatopancreas histology was changed significantly. Transcriptomic analysis showed that a total of 4302, 3651, and 4830 differentially expressed genes (DEGs) were identified at 3, 12, and 48 h following NP exposure. All these DEGs were classified into 12 clusters according to the expression patterns at different time points. GO and KEGG enrichment analyses of DEGs were also performed, immunological, metabolic, and inflammatory related pathways, including arachidonic acid metabolism (ko00590), the PPAR signaling pathway (ko03320), and the regulation of TRP channels by inflammatory mediators (ko04750) were significantly enriched. Six DEGs were selected for validation by quantitative real-time PCR (qRT-PCR) and the results confirmed the reliability of transcriptome data. All results indicated that NP is toxic to L. vannamei by damaging the histopathological structure and disrupting the biological function. The findings would provide a theoretical framework for lowering or limiting the detrimental impacts of NP on aquaculture and help us to further study the molecular toxicity of NP in crustaceans.

Investigating higher-order interactions in single-cell data with scHOT.

Single-cell genomics has transformed our ability to examine cell fate choice. Examining cells along a computationally ordered 'pseudotime' offers the potential to unpick subtle changes in variability and covariation among key genes. We describe an approach, scHOT-single-cell higher-order testing-which provides a flexible and statistically robust framework for identifying changes in higher-order interactions among genes. scHOT can be applied for cells along a continuous trajectory or across space and accommodates various higher-order measurements including variability or correlation. We demonstrate the use of scHOT by studying coordinated changes in higher-order interactions during embryonic development of the mouse liver. Additionally, scHOT identifies subtle changes in gene-gene correlations across space using spatially resolved transcriptomics data from the mouse olfactory bulb. scHOT meaningfully adds to first-order differential expression testing and provides a framework for interrogating higher-order interactions using single-cell data.

Heterocyclic Boron Acid Catalyzed Dehydrative Amidation of Aliphatic/Aromatic Carboxylic Acids with Amines.

A commercially available and versatile dehydrative amidation catalyst, featuring a thianthrene boron acid structure, has been developed. The catalyst shows high catalytic activity to both aliphatic and less reactive aromatic carboxylic acid substrates, including several bioactive or clinical molecules with a carboxylic acid group.

scMerge leverages factor analysis, stable expression, and pseudoreplication to merge multiple single-cell RNA-seq datasets.

Concerted examination of multiple collections of single-cell RNA sequencing (RNA-seq) data promises further biological insights that cannot be uncovered with individual datasets. Here we present scMerge, an algorithm that integrates multiple single-cell RNA-seq datasets using factor analysis of stably expressed genes and pseudoreplicates across datasets. Using a large collection of public datasets, we benchmark scMerge against published methods and demonstrate that it consistently provides improved cell type separation by removing unwanted factors; scMerge can also enhance biological discovery through robust data integration, which we show through the inference of development trajectory in a liver dataset collection.

DeepAntigen: a novel method for neoantigen prioritization via 3D genome and deep sparse learning.

MOTIVATION: The mutations of cancers can encode the seeds of their own destruction, in the form of T-cell recognizable immunogenic peptides, also known as neoantigens. It is computationally challenging, however, to accurately prioritize the potential neoantigen candidates according to their ability of activating the T-cell immunoresponse, especially when the somatic mutations are abundant. Although a few neoantigen prioritization methods have been proposed to address this issue, advanced machine learning model that is specifically designed to tackle this problem is still lacking. Moreover, none of the existing methods considers the original DNA loci of the neoantigens in the perspective of 3D genome which may provide key information for inferring neoantigens' immunogenicity. RESULTS: In this study, we discovered that DNA loci of the immunopositive and immunonegative MHC-I neoantigens have distinct spatial distribution patterns across the genome. We therefore used the 3D genome information along with an ensemble pMHC-I coding strategy, and developed a group feature selection-based deep sparse neural network model (DNN-GFS) that is optimized for neoantigen prioritization. DNN-GFS demonstrated increased neoantigen prioritization power comparing to existing sequence-based approaches. We also developed a webserver named deepAntigen (http://yishi.sjtu.edu.cn/deepAntigen) that implements the DNN-GFS as well as other machine learning methods. We believe that this work provides a new perspective toward more accurate neoantigen prediction which eventually contribute to personalized cancer immunotherapy. AVAILABILITY AND IMPLEMENTATION: Data and implementation are available on webserver: http://yishi.sjtu.edu.cn/deepAntigen. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Mutational and transcriptomic landscapes of a rare human prostate basal cell carcinoma.

BACKGROUND: As a rare subtype of prostate carcinoma, basal cell carcinoma (BCC) has not been studied extensively and thus lacks systematic molecular characterization. METHODS: Here, we applied single-cell genomic amplification and RNA-Seq to a specimen of human prostate BCC (CK34ßE12+ /P63+ /PAP- /PSA- ). The mutational landscape was obtained via whole exome sequencing of the amplification mixture of 49 single cells, and the transcriptomes of 69 single cells were also obtained. RESULTS: The five putative driver genes mutated in BCC are CASC5, NUTM1, PTPRC, KMT2C, and TBX3, and the top three nucleotide substitutions are C>T, T>C, and C>A, similar to common prostate cancer. The distribution of the variant allele frequency values indicated that these single cells are from the same tumor clone. The 69 single cells were clustered into tumor, stromal, and immune cells based on their global transcriptomic profiles. The tumor cells specifically express basal cell markers like KRT5, KRT14, and KRT23 and epithelial markers EPCAM, CDH1, and CD24. The transcription factor covariance network analysis showed that the BCC tumor cells have distinct regulatory networks. By comparison with current prostate cancer datasets, we found that some of the bulk samples exhibit basal cell signatures. Interestingly, at single-cell resolution the gene expression patterns of prostate BCC tumor cells show uniqueness compared with that of common prostate cancer-derived circulating tumor cells. CONCLUSIONS: This study, for the first time, discloses the comprehensive mutational and transcriptomic landscapes of prostate BCC, which lays a foundation for the understanding of its tumorigenesis mechanism and provides new insights into prostate cancers in general.

Single-cell analyses reveal functional classification of dendritic cells and their potential roles in inflammatory disease.

Dendritic cells (DCs) have crucial roles in immune-related diseases. However, it is difficult to explore DCs because of their rareness and heterogeneity. Although previous studies had been performed to detect the phenotypic characteristics of DC populations, the functional diversity has been ignored. Using a combination of flow cytometry, single-cell quantitative PCR, and bioinformatic analysis, we depicted the DC panorama with not only phenotypic but also functional markers. Functional classification of DCs in mouse lymphoid tissue (spleen) and nonlymphoid tissue (liver) was performed. The results revealed that expression of macrophage scavenger receptor 1 ( MSR1) and C-C motif chemokine receptors ( CCR) 1, CCR2, and CCR4 were elevated in liver DCs, suggesting increased lipid uptake and migration abilities. The enriched expression of costimulatory molecule CD80, TLR9, and TLR adaptor MYD88 in spleen DCs indicated a more-mature phenotype, enhanced pathogen recognition, and T-cell stimulation abilities. Furthermore, we compared DCs in the atherosclerotic mouse models with healthy controls. In addition to the quantitative increase in DCs in the liver and spleen of the apolipoprotein E-knockout ( ApoE-/-) mice, the functional expression patterns of the DCs also changed at the single-cell level. These results promote our understanding of the participation of DCs in inflammatory diseases and have potential applications in DC clinical assessment.-Shi, Q., Zhuang, F., Liu, J.-T., Li, N., Chen, Y.-X., Su, X.-B., Yao, A.-H., Yao, Q.-P., Han, Y., Li, S.-S., Qi, Y.-X., Jiang, Z.-L. Single-cell analyses reveal functional classification of dendritic cells and their potential roles in inflammatory disease.

Conditional knockin of Dnmt3a R878H initiates acute myeloid leukemia with mTOR pathway involvement.

DNMT3A is frequently mutated in acute myeloid leukemia (AML). To explore the features of human AML with the hotspot DNMT3A R882H mutation, we generated Dnmt3a R878H conditional knockin mice, which developed AML with enlarged Lin-Sca1+cKit+ cell compartments. The transcriptome and DNA methylation profiling of bulk leukemic cells and the single-cell RNA sequencing of leukemic stem/progenitor cells revealed significant changes in gene expression and epigenetic regulatory patterns that cause differentiation arrest and growth advantage. Consistent with leukemic cell accumulation in G2/M phase, CDK1 was up-regulated due to mTOR activation associated with DNA hypomethylation. Overexpressed CDK1-mediated EZH2 phosphorylation resulted in an abnormal trimethylation of H3K27 profile. The mTOR inhibitor rapamycin elicited a significant therapeutic response in Dnmt3aR878H/WT mice.

Application of qPCR assays based on haloacids transporter gene dehp2 for discrimination of Burkholderia and Paraburkholderia.

BACKGROUND: A major facilitator superfamily transporter Dehp2 was recently shown to be playing an important role in transport and biodegradation of haloacids in Paraburkholderia caribensis MBA4, and Dehp2 is phylogenetically conserved in Burkholderia sensu lato. RESULTS: We designed both Burkholderia sensu stricto-specific and Paraburkholderia-specific qPCR assays based on dehp2 and 16S rRNA, and validated the qPCR assays in 12 bacterial strains. The qPCR assays could detect single species of Burkholderia sensu stricto or Paraburkholderia with high sensitivity and discriminate them in mixtures with high specificity over a wide dynamic range of relative concentrations. At relatively lower cost compared with sequencing-based approach, the qPCR assays will facilitate discrimination of Burkholderia sensu stricto and Paraburkholderia in a large number of samples. CONCLUSIONS: For the first time, we report the utilization of a haloacids transporter gene for discriminative purpose in Burkholderia sensu lato. This enables not only quick decision on proper handling of putative pathogenic samples in Burkholderia sensu stricto group but also future exploitation of relevant species in Paraburkholderia group for haloacids biodegradation purposes.

Cancer type prediction based on copy number aberration and chromatin 3D structure with convolutional neural networks.

BACKGROUND: With the developments of DNA sequencing technology, large amounts of sequencing data have been produced that provides unprecedented opportunities for advanced association studies between somatic mutations and cancer types/subtypes which further contributes to more accurate somatic mutation based cancer typing (SMCT). In existing SMCT methods however, the absence of high-level feature extraction is a major obstacle in improving the classification performance. RESULTS: We propose DeepCNA, an advanced convolutional neural network (CNN) based classifier, which utilizes copy number aberrations (CNAs) and HiC data, to address this issue. DeepCNA first pre-process the CNA data by clipping, zero padding and reshaping. Then, the processed data is fed into a CNN classifier, which extracts high-level features for accurate classification. Experimental results on the COSMIC CNA dataset indicate that 2D CNN with both cell lines of HiC data lead to the best performance. We further compare DeepCNA with three widely adopted classifiers, and demonstrate that DeepCNA has at least 78% improvement of performance. CONCLUSIONS: This paper demonstrates the advantages and potential of the proposed DeepCNA model for processing of somatic point mutation based gene data, and proposes that its usage may be extended to other complex genotype-phenotype association studies.

Transport of haloacids across biological membranes.

Haloacids are considered to be environmental pollutants, but some of them have also been tested in clinical research. The way that haloacids are transported across biological membranes is important for both biodegradation and drug delivery purposes. In this review, we will first summarize putative haloacids transporters and the information about haloacids transport when studying carboxylates transporters. We will then introduce MCT1 and SLC5A8, which are respective transporter for antitumor agent 3-bromopyruvic acid and dichloroacetic acid, and monochloroacetic acid transporters Deh4p and Dehp2 from a haloacids-degrading bacterium. Phylogenetic analysis of these haloacids transporters and other monocarboxylate transporters reveals their evolutionary relationships. Haloacids transporters are not studied to the extent that they deserve compared with their great application potentials, thus future inter-discipline research are desired to better characterize their transport mechanisms for potential applications in both environmental and clinical fields.

Single-cell RNA-Seq analysis reveals dynamic trajectories during mouse liver development.

BACKGROUND: The differentiation and maturation trajectories of fetal liver stem/progenitor cells (LSPCs) are not fully understood at single-cell resolution, and a priori knowledge of limited biomarkers could restrict trajectory tracking. RESULTS: We employed marker-free single-cell RNA-Seq to characterize comprehensive transcriptional profiles of 507 cells randomly selected from seven stages between embryonic day 11.5 and postnatal day 2.5 during mouse liver development, and also 52 Epcam-positive cholangiocytes from postnatal day 3.25 mouse livers. LSPCs in developing mouse livers were identified via marker-free transcriptomic profiling. Single-cell resolution dynamic developmental trajectories of LSPCs exhibited contiguous but discrete genetic control through transcription factors and signaling pathways. The gene expression profiles of cholangiocytes were more close to that of embryonic day 11.5 rather than other later staged LSPCs, cuing the fate decision stage of LSPCs. Our marker-free approach also allows systematic assessment and prediction of isolation biomarkers for LSPCs. CONCLUSIONS: Our data provide not only a valuable resource but also novel insights into the fate decision and transcriptional control of self-renewal, differentiation and maturation of LSPCs.

Existence of a robust haloacid transport system in a Burkholderia species bacterium.

Bacterium Burkholderia sp. MBA4 can utilize haloacids as the sole carbon and energy source for growth. We have previously reported that a haloacid operon, encoding for a dehalogenase (Deh4a) and an associated permease (Deh4p), was responsible for the transformation and uptake of haloacids in MBA4. A disruption of deh4p in MBA4 caused a decrease in monochloroacetate (MCA) uptake, confirming its role as a haloacid transporter. However, this disruptant retained 68% of its MCA-uptake activity indicating the possibility of an alternative system. In this study, we report the identification of a second MCA-inducible haloacid transporter (Dehp2) in MBA4. Its function was confirmed by gene disruption and heterologous expression in Escherichia coli. A dehp2(-) mutant has 30% less, and an E. coli expressing Dehp2 has 40% more, of wildtype MCA-uptake activity. Quantitative RT-PCR illustrated that the minor loss of MCA-uptake activity in single disruptants of deh4p and dehp2 was partly due to a compensatory expression of the alternative gene. Competition assay and kinetics study revealed that Deh4p has a higher affinity for MCA while Dehp2 prefers chloropropionate. A deh4p(-)dehp2(-) double mutant retained 36% of MCA-uptake activity, indicating a robustness of the haloacid uptake systems. The MCA uptake activities mediated by Deh4p, Dehp2 and the uncharacterized system were completely abolished by protonophore carbonyl cyanide 3-chlorophenylhydrazone, suggesting that transmembrane electrochemical gradient is the driving force for MCA uptake.

Comparative Transcriptome Analysis of the Hepatopancreas from Macrobrachium rosenbergii Exposed to the Heavy Metal Copper.

The contamination of aquatic ecosystems by the heavy metal copper (Cu) is an important environmental issue and poses significant risks to the physiological functions of aquatic organisms. Macrobrachium rosenbergii is one of the most important freshwater-cultured prawns in the world. The hepatopancreas of crustaceans is a key organ for immune defense, heavy metal accumulation, and detoxification, playing a pivotal role in toxicological research. However, research on the molecular response of the hepatopancreas in M. rosenbergii to Cu exposure is still lacking. In this study, the transcriptomic response in the hepatopancreas of M. rosenbergii was studied after Cu exposure for 3 and 48 h. Compared with the control group, 11,164 (7288 up-regulated and 3876 down-regulated genes) and 10,937 (6630 up-regulated and 4307 down-regulated genes) differentially expressed genes (DEGs) were identified after 3 and 48 h exposure, respectively. Most of these DEGs were up-regulated, implying that gene expressions were largely induced by Cu. Functional enrichment analysis of these DEGs revealed that immunity, copper homeostasis, detoxification, DNA damage repair, and apoptosis were differentially regulated by Cu. Seven genes involved in immunity, detoxification, and metabolism were selected for validation by qRT-PCR, and the results confirmed the reliability of RNA-Seq. All these findings suggest that M. rosenbergii attempts to resist the toxicity of Cu by up-regulating the expression of genes related to immunity, metabolism, and detoxification. However, with the excessive accumulation of reactive oxygen species (ROS), the antioxidant enzyme system was destroyed. As a result, DNA damage repair and the cellular stress response were inhibited, thereby exacerbating cell damage. In order to maintain the normal function of the hepatopancreas, M. rosenbergii removes damaged cells by activating the apoptosis mechanism. Our study not only facilitates an understanding of the molecular response mechanisms of M. rosenbergii underlying Cu toxicity effects but also helps us to identify potential biomarkers associated with the stress response in other crustaceans.

Gene doping detection in the era of genomics.

Recent progress in gene editing has enabled development of gene therapies for many genetic diseases, but also made gene doping an emerging risk in sports and competitions. By delivery of exogenous transgenes into human body, gene doping not only challenges competition fairness but also places health risk on athletes. World Anti-Doping Agency (WADA) has clearly inhibited the use of gene and cell doping in sports, and many techniques have been developed for gene doping detection. In this review, we will summarize the main tools for gene doping detection at present, highlight the main challenges for current tools, and elaborate future utilizations of high-throughput sequencing for unbiased, sensitive, economic and large-scale gene doping detections. Quantitative real-time PCR assays are the widely used detection methods at present, which are useful for detection of known targets but are vulnerable to codon optimization at exon-exon junction sites of the transgenes. High-throughput sequencing has become a powerful tool for various applications in life and health research, and the era of genomics has made it possible for sensitive and large-scale gene doping detections. Non-biased genomic profiling could efficiently detect new doping targets, and low-input genomics amplification and long-read third-generation sequencing also have application potentials for more efficient and straightforward gene doping detection. By closely monitoring scientific advancements in gene editing and sport genetics, high-throughput sequencing could play a more and more important role in gene detection and hopefully contribute to doping-free sports in the future.

Biochemical, histological and transcriptional response of intestines in Litopenaeus vannamei under chronic zinc exposure.

Zinc (Zn) is an essential trace element for the normal physiological function of aquatic organisms, but it could become toxic to organisms when the concentration increased in water. As the first line of defense, the shrimp intestines are the most susceptible organ to environmental stress. In this study, the chronic toxicity of 0 (control, IC), 0.01(IL), 0.1(IM) and 1 mg/L (IH) Zn in intestines of Litopenaeus vannamei was investigated from the perspectives of biochemical, histological and transcriptional changes after exposure for 30 days. The results showed that the intestinal tissue basement membrane is swollen in the IM and IH groups and detached in the IH group. The total antioxidant capacities (T-AOC) were reduced while the content of malondialdehyde (MDA) were increased significantly in IM and IH groups. The production of reactive oxygen species (ROS) was increased significantly in IH group. Many differentially expressed genes (DEGs) were identified in IL, IM and IH groups, respectively. GO and KEGG enrichment analyses were conducted on the DEGs to obtain the underlying biological processes and pathways. The gene modules related to the sample were identified by weighted gene co-expression network analysis (WGCNA), and genes in modules highly corelated with IH group were mainly enriched in immune related pathways. Nine DEGs were selected for validation by quantitative real time PCR (qRT-PCR) and the expression profiles of these DEGs kept a well consistent with the high-throughput data, which confirmed reliability of transcriptome results. Additionally, 10 DEGs were screened to detect the changes of expression level in different groups. All these results indicated that Zn exposure could damage the intestinal barrier, provoke oxidative stress, reduce the immune function, increase the susceptibility to bacterial infections of L. vannamei and cause inflammation, ultimately result in cell apoptosis. Our study provides more perspective on the stress response of crustacean under Zn exposure.

Enhanced degradation of haloacid by heterologous expression in related Burkholderia species.

Haloacids are environmental pollutant and can be transformed to non-toxic alkanoic acids by microbial dehalogenase. Bacterium Burkholderia species MBA4 was enriched from soil for its ability to bioremediate haloacids such as mono-chloroacetate (MCA), mono-bromoacetate (MBA), 2-mono-chloropropionate, and 2-mono-bromopropionate. MBA4 produces an inducible dehalogenase Deh4a that catalyzes the dehalogenation process. The growth of MBA4 on haloacid also relies on the presence of a haloacid-uptake system. Similar dehalogenase genes can be found in the genome of many related species. However, wildtype Burkholderia caribensis MWAP64, Burkholderia phymatum STM815, and Burkholderia xenovorans LB400 were not able to grow on MCA. When a plasmid containing the regulatory and structural gene of Deh4a was transformed to these species, they were able to grow on haloacid. The specific enzyme activities in these recombinants ranges from 2- to 30-fold that of MBA4 in similar condition. Reverse transcription-quantitative real-time PCR showed that the relative transcript levels in these recombinant strains ranges from 9 to over 1,600 times that of MBA4 in similar condition. A recombinant has produced nearly five times of dehalogenase that MBA4 could ever achieve. While the expressions of Deh4a were more relaxed in these phylogenetically related species, an MCA-uptake activity was found to be inducible. These metabolically engineered strains are better degraders than the haloacid-enriched MBA4.

Heavy metal contamination in Shanghai agricultural soil.

As heavy metals in soil could enrich in biomass and pose health risk to human, it is vital to monitor their contaminations to ensure qualified agricultural production. In this study, we collected >4000 soil samples from agricultural fields in Shanghai during 2010∼2020, and unveiled heavy metal contamination status in this metropolitan. We found that although Shanghai has a long industrialization history, the heavy metal levels in agricultural soil are within safe ranges according to national standard. Specifically, the median levels of Cd, Hg, As, Pb, Cr and Cu are 0.11, 0.13, 7.47, 23.80, 41.00 and 28.30 mg/kg, respectively, which are as good as, or even better than national averages. However, there are spatial and temporal heterogeneities for heavy metal contaminations in Shanghai. For example, the levels of Cd, Hg and Cr are relatively higher in some districts with high industry density, which should be further monitored in the future. Moreover, while the levels for Cd, Cr and Pb have decreased, the level for Hg has mildly increased during this period which needs counteractive measures. Correlation analysis of heavy metal levels and soil fertility parameters suggested overuse of fertilizers may be related to heavy metal contamination in some regions. In summary, our study present by far the largest and most comprehensive landscape of heavy metal contamination in Shanghai agricultural soil, which will be useful for future policy-design and land use planning to ensure safe agricultural production.