Biology subjects

Wang, B.

Publications and source records attributed to Wang, B..

At least 631 records · Page 35Linked to original sources

bioRxiv2020

BAP31 regulated polarization of macrophages through C/EBP β in cutaneous wound healing

The functions carried out by macrophages are essential in the processes of repairing skin injury. However, the mechanism of the M2 macrophage and its role in cutaneous wound healing remain elusive. B cell receptor associated protein 31 (BAP31) plays an important role in the immune system, and its function in connection with macrophages has yet to be determined. The present study demonstrates that the process of cutaneous wound healing slowed down in bone marrow-specific BAP31 knock down Lyz2-cre-BAP31flox/flox mice. In addition, further studies show that various kinds of macrophage M2 polarization related factors were regulated by BAP31. Among these molecules C/EBP {beta} was significantly affected. However, IL-4 but not IFN-{gamma}, is able to recover the expression levels of C/EBP {beta} and its downstream transcript factors induced by BAP31. Then, we demonstrated that BAP31 regulated macrophage M2 polarization by negative regulation of IL-4R and positive influence on Egr-2 to affect C/EBP {beta}. Our findings reveal a novel mechanism of BAP31 in regulating M2 macrophage, and provide novel targets for the prevention and treatment of chronic wounds.

molecular biology↗

bioRxiv2020

SORBS2 is a genetic factor contributing to cardiac malformation of 4q deletion syndrome

Chromosome 4q deletion is one of the most frequently detected genomic imbalance events in congenital heart disease (CHD) patients. However, a portion of CHD-associated 4q deletions do not include known CHD genes. Alignment of those 4q deletions defined a minimal overlapping region including only one gene-SORBS2. Histological analysis of Sorbs2-/- heart revealed atrial septal hypoplasia/aplasia or double atrial septum. Mechanistically, SORBS2 had a dual role in maintaining sarcomeric integrity of cardiomyocytes and specifying the fate of second heart field (SHF) progenitors through c-ABL/NOTCH/SHH axis. In a targeted sequencing of a panel of known and candidate CHD genes on 300 CHD cases, we found that rare SORBS2 variants were significantly enriched in CHD patients. Our findings indicate that SORBS2 is a regulator of cardiac development and its haploinsufficiency may contribute to cardiac phenotype of 4q deletion syndrome. The presence of double atrial septum in Sorbs2-/- hearts reveals the first molecular etiology of this rare anomaly linked to paradoxical thromboembolism.

genetics↗

bioRxiv2020

Single cell fitness landscapes induced by genetic and pharmacologic perturbations in cancer

Tumour fitness landscapes underpin selection in cancer, impacting etiology, evolution and response to treatment. Progress in defining fitness landscapes has been impeded by a lack of timeseries perturbation experiments over realistic intervals at single cell resolution. We studied the nature of clonal dynamics induced by genetic and pharmacologic perturbation with a quantitative fitness model developed to ascribe quantitative selective coefficients to individual cancer clones, enable prediction of clone-specific growth potential, and forecast competitive clonal dynamics over time. We applied the model to serial single cell genome (>60,000 cells) and transcriptome (>58,000 cells) experiments ranging from 10 months to 2.5 years in duration. We found that genetic perturbation of TP53 in epithelial cell lines induces multiple forms of copy number alteration that confer increased fitness to clonal populations with measurable consequences on gene expression. In patient derived xenografts, predicted selective coefficients accurately forecasted clonal competition dynamics, that were validated with timeseries sampling of experimentally engineered mixtures of low and high fitness clones. In cisplatin-treated patient derived xenografts, the fitness landscape was inverted in a time-dependent manner, whereby a drug resistant clone emerged from a phylogenetic lineage of low fitness clones, and high fitness clones were eradicated. Moreover, clonal selection mediated reversible drug response early in the selection process, whereas late dynamics in genomically fixed clones were associated with transcriptional plasticity on a fixed clonal genotype. Together, our findings outline causal mechanisms with implication for interpreting how mutations and multi-faceted drug resistance mechanisms shape the etiology and cellular fitness of human cancers.

cancer biology↗

bioRxiv2020

Single-cell longitudinal analysis of SARS-CoV-2 infection in human bronchial epithelial cells

SARS-CoV-2, the causative agent of COVID-19, has tragically burdened individuals and institutions around the world. There are currently no approved drugs or vaccines for the treatment or prevention of COVID-19. Enhanced understanding of SARS-CoV-2 infection and pathogenesis is critical for the development of therapeutics. To reveal insight into viral replication, cell tropism, and host-viral interactions of SARS-CoV-2 we performed single-cell RNA sequencing of experimentally infected human bronchial epithelial cells (HBECs) in air-liquid interface cultures over a time-course. This revealed novel polyadenylated viral transcripts and highlighted ciliated cells as a major target of infection, which we confirmed by electron microscopy. Over the course of infection, cell tropism of SARS-CoV-2 expands to other epithelial cell types including basal and club cells. Infection induces cell-intrinsic expression of type I and type III IFNs and IL6 but not IL1. This results in expression of interferon-stimulated genes in both infected and bystander cells. We observe similar gene expression changes from a COVID-19 patient ex vivo. In addition, we developed a new computational method termed CONditional DENSity Embedding (CONDENSE) to characterize and compare temporal gene dynamics in response to infection, which revealed genes relating to endothelin, angiogenesis, interferon, and inflammation-causing signaling pathways. In this study, we conducted an in-depth analysis of SARS-CoV-2 infection in HBECs and a COVID-19 patient and revealed genes, cell types, and cell state changes associated with infection.

microbiology↗

bioRxiv2020

Three-dimensional Genome Organization Maps in Normal Haematopoietic Stem Cells and Acute Myeloid Leukemia

Acute Myeloid Leukemia (AML) is a highly lethal blood cancer arising due to aberrant differentiation of haematopoietic stem cells. Here we obtained 3D genome organization maps by Hi-C in the CD34+ haematopoietic stem cells from three healthy individuals and eight individuals with AML, and found that AML have increased loops to oncogenes compared with normal CD34+ cells. The MEIS1 oncogenic transcription factor is regulated by a Frequently Interacting Region (FIRE). This FIRE is only present in normal bone marrow samples, and four of eight AML sample. FIRE presence is associated with MEIS1 expression. CRISPR excision of a FIRE boundary led to loss of MEIS1 and reduced cell growth. Moreover, MEIS1 can bind to the promoter of HOXA9, and HOXA9 shows gain of Acute Myeloid Leukemia-specific super-enhancers that loop to the HOXA9 promoter. SignificanceWe found that Acute Myeloid Leukemias have more chromatin loops to oncogenes compared with normal blood stem cells. We identified heterogeneity in chromatin interactions at oncogenes, and heterogeneity in super-enhancers that loop to oncogenes, as two key epigenetic mechanisms that underlie MEIS1 and HOXA9 oncogene expression respectively.

cancer biology↗

bioRxiv2020

Studies on trans-sutural distraction osteogenesis-related genes based on transcriptome sequencing

Trans-sutural distraction osteogenesis (TSDO) is an important approach to improve mid-face hypoplasia. In recent years, many studies have been carried out on physical mechanisms of TSDO; however, its specific cytological and molecular mechanisms are still unclear. In this study, we performed transcriptome sequencing analysis in Sprague Dawley rats at 1 and 2 weeks after suture osteogenesis and compared RNA expression levels between experimental and control groups. At one week, enrichment pathways were mainly up-regulated in muscle- and bone-related pathways. By contrast, pathways of the immune system showed a state of inhibition and down-regulation, especially for B cells; the main immune pathways showed significant down-regulation. However, two weeks later, the experimental group showed positive up-regulation of the pathways related to DNA synthesis and replication, cell cycle, and chromosome replication. At the same time, the immune pathways that were down-regulated in the first week were up-regulated in the second week. In other words, the up-regulated muscle- and bone-related pathways show opposite trends. The expression of bone- and myogenesis-related transcriptome was up-regulated and the immune-related pathways were down-regulated in the experimental group at 1 week. At 2 weeks, the pathways related to bone- and muscle were down-regulated, while those related to cell cycle regulation and DNA replication were up-regulated. These results suggest that musculoskeletal-related molecules may play an important role during suture osteogenesis at 1 week, and immune regulation may be involved in this process; however, at 2 weeks, molecules related to cell proliferation and replication may be a major role.

bioinformatics↗

bioRxiv2020

CNSA: a data repository for archiving omics data

With the application and development of high-throughput sequencing technology in life and health sciences, massive multi-dimensional biological data brings the problem of efficient management and utilization. Database development and biocuration are the prerequisites for the reuse of these big data. Here, relying on China National GeneBank (CNGB), we present CNGB Sequence Archive (CNSA) for archiving omics data, including raw sequencing data and its analytical data and related metadata which are organized into six objects, namely Project, Sample, Experiment, Run, Assembly, and Variation at present. Moreover, CNSA has created the correlation model of living samples, sample information, and analytical data on some projects, so that all data can be traced throughout the life cycle from the living sample to the sample information to the analytical data. Complying with the data standards commonly used in the life sciences, CNSA is committed to building a comprehensive and curated data repository for the storage, management and sharing of omics data, improving the data standards, and providing free access to open data resources for worldwide scientific communities to support academic research and the bio-industry. Database URL: https://db.cngb.org/cnsa/

genomics↗

bioRxiv2020

A high-throughput platform for feedback-controlled directed evolution.

Continuous directed evolution rapidly implements cycles of mutagenesis, selection, and replication to accelerate protein engineering. However, individual experiments are typically cumbersome, reagent-intensive, and require manual readjustment, limiting the number of evolutionary trajectories that can be explored. We report the design and validation of Phage-and-Robotics-Assisted Near-Continuous Evolution (PRANCE), an automation platform for the continuous directed evolution of biomolecules that enables real-time activitydependent reporter and absorbance monitoring of up to 96 parallel evolution experiments. We use this platform to characterize the evolutionary stochasticity of T7 RNA polymerase evolution, conserve precious reagents with miniaturized evolution volumes during evolution of aminoacyl-tRNA synthetases, and perform a massively parallel evolution of diverse candidate quadruplet tRNAs. Finally, we implement a feedback control system that autonomously modifies the selection strength in response to real-time fitness measurements. By addressing many of the limitations of previous methods within a single platform, PRANCE simultaneously enables multiplexed, miniaturized, and feedback-controlled continuous directed evolution.

bioengineering↗

bioRxiv2020

Induction of hyperandrogenism and insulin resistance differentially modulates ferroptosis in uterine and placental tissues of pregnant rats

Ferroptosis, a form of regulated necrotic cell death, plays roles in diverse physiological processes and diseases. Women with polycystic ovary syndrome (PCOS) have hyperandrogenism and insulin resistance (HAIR) and an increased risk of miscarriage and placental dysfunction during pregnancy. However, whether maternal HAIR alters mechanisms leading to ferroptosis in the gravid uterus and placenta remains unknown. Previous studies in rats showed that maternal exposure to 5-dihydrotestosterone (DHT) and insulin (INS) from gestational day 7.5 to 13.5 induces HAIR and subsequently leads to placental insufficiency and fetal loss. We therefore hypothesized that maternal HAIR triggers ferroptosis in the uterus and placenta in association with fetal loss in pregnant rats. Compared with controls, we found that co-exposure to DHT and INS led to decreased levels of Gpx4 and glutathione (GSH), increased GSH+glutathione disulfide (GSSG) and malondialdehyde (MDA), aberrant expression of ferroptosis-associated genes (Acsl4, Tfrc, Slc7a11, and Gclc), increased iron deposition, and activated ERK/p38/JNK phosphorylation in the gravid uterus. However, in the placenta, DHT and INS exposure only partially altered the expression of ferroptosis-related markers (e.g., region-dependent Gpx4, GSH+GSSG, MDA, Gls2 and Slc7a11 mRNAs, and phosphorylated p38 levels). In the uteri co-exposed to DHT and INS, we also observed shrunken mitochondria with electron-dense cristae, which are key features of ferroptosis-related mitochondrial morphology, as well as increased expression of Dpp4, a mitochondria-encoded gene responsible for ferroptosis induction. In contrast, in placentas co-exposed to DHT and INS we found decreased expression of Dpp4 mRNA and increased expression of Cisd1 mRNA (a mitochondria-encoded iron-export factor). Further, DHT+INS-exposed pregnant rats exhibited decreased apoptosis in the uterus and increased necroptosis in the placenta. Our findings suggest that maternal HAIR causes the activation of ferroptosis in the gravid uterus and placenta, although this is mediated via different mechanisms operating at the molecular and cellular levels. Furthermore, our data suggest other cell death pathways may play a role in coordinating or compensating for HAIR-induced ferroptosis when the gravid uterus and placenta are dysfunctional. Suppl Figures: https://doi.org/10.6084/m9.figshare.11794059.v5

physiology↗

bioRxiv2020

Partnership between epigenetic reader BRD4 and transcription factor CEBPD

Vascular smooth muscle cell (SMC) state/phenotype transitions underlie neointimal hyperplasia (IH) predisposing to cardiovascular diseases. Bromodomain protein BRD4 is a histone acetylation reader and enhancer mark that co-activates transcription elongation. CCAAT enhancer binding protein delta (CEBPD) is a transcription factor typically studied in adipogenesis and immune cell differentiation. Here we investigated the association between BRD4 and CEBPD in SMC state transition. Chromatin immunoprecipitation sequencing (ChIPseq) showed enrichment of BRD4 and histone acetylation (H3K27ac) at Cebpd and enhancer in rat carotid arteries undergoing IH. In vitro, BRD4 silencing with siRNA reduced SMC expression of CEBPD. Bromodomain-1 but not bromodoamin-2 accounted for this BRD4 function. Endogenous BRD4 co-IPed with CEBPD; Cebpd promoter and enhancer DNA fragments co-IPed with CEBPD or endogenous BRD4 (ChIP-qPCR). These co-IPs were abolished by the BRD4 bromodomain blocker JQ1. TNF upregulated both BRD4 and CEBPD. Silencing CEBPD averted TNF-induced inflammatory SMC state transition (heightened IL-1{beta}, IL6, and MCP-1 mRNA levels), so did JQ1. CEBPD overexpression increased PDGFR preferentially over PDGFR{beta}; so did TNF, and JQ1 abolished TNFs effect. Our data reveal a BRD4/CEBPD partnership that promotes CEBPDs own transcription and inflammatory SMC state transition, thus shedding new light on epigenetic reader and transcription factor cooperative actions in SMC pathobiology.

cell biology↗

bioRxiv2020

Monodisperse drops templated by 3D-structured microparticles

The ability to create uniform sub-nanoliter compartments using microfluidic control has enabled new approaches for analysis of single cells and molecules. However, specialized instruments or expertise have been required, slowing the adoption of these cutting-edge applications. Here, we show that 3D-structured microparticles with sculpted surface chemistries template uniformly-sized aqueous drops when simply mixed with two immiscible fluid phases. In contrast to traditional emulsions, particle-templated drops of a controlled volume occupy a minimum in the interfacial energy of the system, such that a stable monodisperse state results with simple and reproducible formation conditions. We describe techniques to manufacture microscale drop-carrier particles and show that emulsions created with these particles prevent molecular exchange, concentrating reactions within the drops, laying a foundation for sensitive compartmentalized assays with minimal instrumentation.

bioengineering↗

bioRxiv2020

Analysis of genetic signatures of tumor microenvironment yields insight into mechanisms of resistance to immunotherapy

BackgroundTherapeutic intervention targeting immune cells have led to remarkable improvements in clinical outcomes of tumor patients. However, responses are not universal. The inflamed tumor microenvironment has been reported to correlate with response in tumor patients. However, due to the lack of appropriate experimental methods, the reason why the immunotherapeutic resistance still existed on the inflamed tumor microenvironment remains unclear. Materials and methodsHere, based on integrated single-cell RNA sequencing technology, we classified tumor microenvironment into inflamed immunotherapeutic responsive and inflamed non-responsive. Then, phenotype-specific genes were identified to show mechanistic differences between distant TME phenotypes. Finally, we screened for some potential favorable TME phenotypes transformation drugs to aid current immunotherapy. ResultsMultiple signaling pathways were phenotypes-specific dysregulated. For example, Interleukin signaling pathways including IL-4 and IL-13 were activated in inflamed TME across multiple tumor types. PPAR signaling pathways and multiple epigenetic pathways were respectively inhibited and activated in inflamed immunotherapeutic non-responsive TME, suggesting a potential mechanism of immunotherapeutic resistance and target for therapy. We also identified some genetic markers of inflamed non-responsive or responsive TME, some of which have shown its potentials to enhance the efficacy of current immunotherapy. ConclusionThese results may contribute to the mechanistic understanding of immunotherapeutic resistance and guide rational therapeutic combinations of distant targeted chemotherapy agents with immunotherapy.

immunology↗

bioRxiv2020

Pan-cancer analysis identified inflamed microenvironment associated multi-omics signatures

BackgroundImmunotherapy has revolutionized cancer therapy. However, responses are not universal. The inflamed tumor microenvironment has been reported to correlate with response in tumor patients. However, how different tumors shape their tumor microenvironment remains a critical unsolved problem. A deeper insight into the molecular characteristics of inflamed tumor microenvironment may be needed. Materials and methodsHere, based on single-cell RNA sequencing technology and TCGA pan-cancer cohort, we investigated multi-omics molecular features of tumor microenvironment phenotypes. Based on single-cell RNA-seq analysis, we classified pan-cancer tumor samples into inflamed or non-inflamed tumor and identified molecular features of these tumors. Analysis of integrating identified gene signatures with a drug-genomic perturbation database identified multiple drugs which may be helpful for converting non-inflamed tumors to inflamed tumors. ResultsOur results revealed several inflamed/non-inflamed tumor microenvironments-specific molecular characteristics. For example, inflamed tumors highly expressed miR-650 and lncRNA including MIR155HG and LINC00426, these tumors showed activated cytokines-related signaling pathways. Interestingly, non-inflamed tumors tended to express several genes related to neurogenesis. Multi-omics analysis demonstrated the neuro phenotype transformation may be induced by hypomethylated promoters of these genes and down-regulated miR-650. Drug discovery analysis revealed histone deacetylase inhibitors may be a potential choice for helping favorable tumor microenvironment phenotype transformation and aiding current immunotherapy. ConclusionOur results provide a comprehensive molecular-level understanding of tumor cell-immune cell interaction and may have profound clinical implications.

immunology↗

bioRxiv2020

Angioplasty-induced epigenomic remodeling entails BRD4 and EZH2 hierarchical regulations

Atherosclerosis is commonly treated with angioplasty which, however, evokes neointimal hyperplasia (IH) and recurrent stenotic diseases. Epigenomic investigation was lacking on post-angioplasty IH. The histone acetylation reader BRD4 and H3K27me3 writer EZH2 are potent epigenetic factors; their relationship is little understood. Through genome-wide survey in the rat angioplasty model, we studied BRD4 and EZH2 functional regulations involved in IH. We performed chromatin immunoprecipitation sequencing (ChIPseq) using rat carotid arteries. While H3K27me3 ChIPseq signal prevalently intensified in balloon-injured (vs uninjured) arteries, BRD4 and H3K27ac became more enriched at Ezh2. Indeed, BRD4-siRNA or CRISPR-deletion of BRD4-associated enhancer abated the smooth muscle cell (SMC) expression of EZH2, and SMC-specific BRD4 knockout in BRD4fl/fl; Myh11CreERT2 mice reduced both H3K27me3 and IH in wire-injured femoral arteries. In accordance, post-angioplasty IH was exacerbated and mitigated, respectively, by lentiviral expression and pharmacological inhibition of EZH2/1; EZH2 (or EZH1) loss- and gain-of-function respectively attenuated and aggravated pro-IH SMC proliferative behaviors. Furthermore, while H3K27me3 ChIPseq signal magnified at P57 and ebbed at Ccnd1 and Uhrf1 after injury, silencing either EZH2 or EZH1 in SMCs up-regulated P57 and down-regulated Ccnd1 and Uhrf1. In summary, our results reveal an upsurge of EZH2/H3K27me3 after angioplasty, BRD4s control over EZH2 expression, and non-redundant EZH2/1 functions. As such, this study unravels angioplasty-induced loci-specific H3K27me3/ac redistribution in the epigenomic landscape rationalizing BRD4/EZH2-governed pro-IH regulations.

pathology↗

bioRxiv2020

Genome-wide Screens Identify Lineage- and Tumor Specific-Genes Modulating MHC-I and MHC-II Immunosurveillance in Human Lymphomas

Tumors frequently subvert MHC class I (MHC-I) peptide presentation to evade CD8+ T cell immunosurveillance. To better define the regulatory networks controlling antigen presentation, we employed genome-wide screening in human diffuse large B cell lymphomas (DLBCLs). This approach revealed dozens of novel genes that positively and negatively modulate MHC-I cell surface levels. Identified genes cluster in multiple pathways including cytokine signaling, mRNA processing, endosomal trafficking, and protein metabolism. Many genes exhibit lymphoma subtype- or tumor-specific MHC-I regulation, and a majority of primary DLBCL tumors display genetic alterations in multiple regulators. We establish that the HSP90 co-chaperone SUGT1 is a major positive regulator of both MHC-I and MHC-II cell surface expression. Further, pharmacological inhibition of two negative regulators of antigen presentation, EZH2 and thymidylate synthase, enhances DLBCL MHC-I presentation. These and other genes represent potential targets for manipulating MHC-I immunosurveillance in cancers, infectious diseases, and autoimmunity.

cancer biology↗

bioRxiv2020

SARS-CoV-2 invades host cells via a novel route: CD147-spike protein

Currently, COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been widely spread around the world; nevertheless, so far there exist no specific antiviral drugs for treatment of the disease, which poses great challenge to control and contain the virus. Here, we reported a research finding that SARS-CoV-2 invaded host cells via a novel route of CD147-spike protein (SP). SP bound to CD147, a receptor on the host cells, thereby mediating the viral invasion. Our further research confirmed this finding. First, in vitro antiviral tests indicated Meplazumab, an anti-CD147 humanized antibody, significantly inhibited the viruses from invading host cells, with an EC50 of 24.86 g/mL and IC50 of 15.16 g/mL. Second, we validated the interaction between CD147 and SP, with an affinity constant of 1.85x10-7M. Co-Immunoprecipitation and ELISA also confirmed the binding of the two proteins. Finally, the localization of CD147 and SP was observed in SARS-CoV-2 infected Vero E6 cells by immuno-electron microscope. Therefore, the discovery of the new route CD147-SP for SARS-CoV-2 invading host cells provides a critical target for development of specific antiviral drugs.

microbiology↗

bioRxiv2020

Rab27b regulates the release, autophagic clearance, and toxicity of alpha-synuclein

Alpha synuclein (syn) is the primary component of proteinaceous aggregates termed Lewy Bodies that pathologically define synucleinopathies including Parkinsons disease (PD) and Dementia with Lewy Bodies (DLB). Syn is hypothesized to spread through the brain in a prion-like fashion by misfolded protein forming a template for aggregation of endogenous syn. The release and uptake of syn from cell to cell are considered important processes for this prion-like spread. Rab27b is one of several GTPases essential to the endosomal-lysosomal pathway and is implicated in protein secretion and clearance but has yet to be characterized in its role in syn spread. In this study, we used a paracrine syn in vitro model to test the impact of Rab27b on syn release, clearance, and toxicity. shRNA-mediated knockdown (KD) of Rab27b increased syn-mediated paracrine toxicity. While Rab27b reduced syn release primarily through non-exosomal pathways, the syn released under KD conditions was of higher molecular weight species by size exclusion chromatography. Rab27b KD increased intracellular insoluble syn levels and led to an accumulation of endogenous LC3 positive puncta. Rab27b KD also decreased LC3 turnover with chloroquine treatment, indicating a defect in autophagic flux. Rab27b protein levels were increased in postmortem human brain lysates from PD and DLB subjects compared to healthy controls. These data indicate a role for Rab27b in the release, clearance, and toxicity of syn and ultimately in the pathogenesis of synucleinopathies.

neuroscience↗

bioRxiv2020

Global Landscape of Native Protein Complexes in Synechocystis sp. PCC 6803

Synechocystis sp. PCC 6803 (hereafter: Synechocystis) is a model organism for studying photosynthesis, energy metabolism, and environmental stress. Though known as the first fully sequenced phototrophic organism, Synechocystis still has almost half of its proteome without functional annotations. In this study, we obtained 291 protein complexes, including 24,092 protein-protein interactions (PPIs) among 2062 proteins by using co-fractionation and LC/MS/MS. The additional level of PPIs information not only revealed the roles of photosynthesis in metabolism, cell motility, DNA repair, cell division, and other physiological processes, but also showed how protein functions vary from bacteria to higher plants due to the changed interaction partner. It also allows us to uncover functions of hypothetical proteins, such as Sll0445, Sll0446, S110447 participating in photosynthesis and cell motility, and Sll1334 regulating the expression of fatty acid. Here we presented the most extensive protein interaction data in Synechocystis so far, which might provide critical insights into the fundamental molecular mechanism in Cyanobacterium.

biochemistry↗