Whole-genome Expression Profiling Research Articles

Endoplasmic reticulum stress-related signatures: a game-changer in prognostic stratification for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) has limited therapeutic options and a poor prognosis. The endoplasmic reticulum (ER) plays a crucial role in tumor progression and response to stress, making it a promising target for HCC stratification. This study aimed to develop a risk stratification model using ER stress-related signatures. We utilized transcriptome data from The Cancer Genome Atlas and Gene Expression Omnibus, which encompass whole-genome expression profiles and clinical annotations. Machine learning algorithms, including the least absolute shrinkage and selection operator, random forest, and support vector machine recursive feature elimination, were applied to the key genes associated with HCC prognosis. A prognostic system was developed using univariate Cox hazard analysis and least absolute shrinkage and selection operator Cox regression, followed by validation using Kaplan-Meier analysis and receiver operating characteristic curves. Tumor immune dysfunction and exclusion tools were used to predict immunotherapy responsiveness. Two distinct clusters associated with ER stress were identified in HCC, each exhibiting unique clinical and biological features. Using a computational approach, a prognostic risk model, namely the ER stress-related signature, was formulated, demonstrating enhanced predictive accuracy compared with that of existing prognostic models. An effective clinical nomogram was established by integrating the risk model with clinicopathological factors. Patients with lower risk scores exhibited improved responsiveness to various chemotherapeutic, targeted, and immunotherapeutic agents. The critical role of ER stress in HCC is highlighted. The ER stress-related signature developed in this study is a powerful tool to assess the risk and clinical treatment of HCC.

The diagnostic value of inflammation-related genes in bronchopulmonary dysplasia

This study aims to explore the diagnostic value of inflammation-related genes in peripheral blood mononuclear cells in bronchopulmonary dysplasia (BPD). By using bioinformatics analysis, three datasets including GSE32472, GSE125873, and GSE220135, which contain whole-genome expression profile data of 251 neonates, were included. The GSE32472 dataset was used as a training dataset to detect differentially expressed genes between non-BPD and BPD neonates in peripheral blood mononuclear cells. The gene enrichment analysis (GSEA) was used to detect the pathway enrichment of up-regulated genes in BPD newborns. The main regulatory factors analysis (MRA) algorithm was used to filter the main regulatory genes in the inflammation-related pathway (GO:0006954). After obtaining the main regulatory genes, the expression of the main regulatory genes in the GSE32472, GSE125873, and GSE220135 datasets was detected. Through the logistic regression model, risk scoring was conducted for neonates, and the risk scores of non-BPD and BPD neonates were compared. Lastly, the classification performance of the model was evaluated using the area under the curve (AUC). The results showed that compared with non-BPD neonates, there were 486 up-regulated genes and 433 down-regulated genes in the peripheral blood mononuclear cells of BPD neonates. The inflammation-related pathway was highly enriched in the up-regulated genes. Ultimately, phospholipase C beta 1 (PLCB1), nidogen 1 (NID1), serum response factor binding protein 1 (SRFBP1), centrosomal protein 72 (CEP72), excision repair cross complementation group 6 like (ERCC6L), and peptidylprolyl isomerase like 1 (PPIL1) were identified as the main regulatory genes. The prediction model's calculation formula for risk score was PLCB1×0.26+NID1×0.97+SRFBP1×1.58+CEP72×(-0.36)+ERCC6L×2.14+PPIL1×0.67. The AUCs in the GSE32472 test dataset, GSE125873 dataset, and GSE220135 dataset were 0.88, 0.86, and 0.89, respectively. This prediction model could distinguish between non-BPD and BPD neonates. In conclusion, the prediction model based on inflammation-related pathway genes has a certain diagnostic value for BPD.

Exploring the dynamic three-dimensional chromatin architecture and transcriptional landscape in goose liver tissues underlying metabolic adaptations induced by a high-fat diet

BackgroundGoose, descendants of migratory ancestors, have undergone extensive selective breeding, resulting in their remarkable ability to accumulate fat in the liver and exhibit a high tolerance for significant energy intake. As a result, goose offers an excellent model for studying obesity, metabolic disorders, and liver diseases in mammals. Although the impact of the three-dimensional arrangement of chromatin within the cell nucleus on gene expression and transcriptional regulation is widely acknowledged, the precise functions of chromatin architecture reorganization during fat deposition in goose liver tissues still need to be fully comprehended.ResultsIn this study, geese exhibited more pronounced changes in the liver index and triglyceride (TG) content following the consumption of the high-fat diet (HFD) than mice without significant signs of inflammation. Additionally, we performed comprehensive analyses on 10 goose liver tissues (5 HFD, 5 normal), including generating high-resolution maps of chromatin architecture, conducting whole-genome gene expression profiling, and identifying H3K27ac peaks in the livers of geese and mice subjected to the HFD. Our results unveiled a multiscale restructuring of chromatin architecture, encompassing Compartment A/B, topologically associated domains, and interactions between promoters and enhancers. The dynamism of the three-dimensional genome architecture, prompted by the HFD, assumed a pivotal role in the transcriptional regulation of crucial genes. Furthermore, we identified genes that regulate chromatin conformation changes, contributing to the metabolic adaptation process of lipid deposition and hepatic fat changes in geese in response to excessive energy intake. Moreover, we conducted a cross-species analysis comparing geese and mice exposed to the HFD, revealing unique characteristics specific to the goose liver compared to a mouse. These chromatin conformation changes help elucidate the observed characteristics of fat deposition and hepatic fat regulation in geese under conditions of excessive energy intake.ConclusionsWe examined the dynamic modifications in three-dimensional chromatin architecture and gene expression induced by an HFD in goose liver tissues. We conducted a cross-species analysis comparing that of mice. Our results contribute significant insights into the chromatin architecture of goose liver tissues, offering a novel perspective for investigating mammal liver diseases.

Epigenetic control on transcription of vernalization genes and whole-genome gene expression profile induced by vernalization in common wheat

Vernalization is necessary for winter wheat to flower. However, it is unclear whether vernalization is also required for spring wheat, which is frequently sown in fall, and what molecular mechanisms underlie the vernalization response in wheat varieties. In this study, we examined the molecular mechanisms that regulate vernalization response in winter and spring wheat varieties. For this purpose, we determined how major vernalization genes (VRN1, VRN2, and VRN3) respond to vernalization in these varieties and whether modifications to histones play a role in changes in gene expression. We also identified genes that are differentially regulated in response to vernalization in winter and spring wheat varieties. We found that in winter wheat, but not in spring wheat, VRN1 expression decreases when returned to warm temperature following vernalization. This finding may be associated with differences between spring and winter wheat in the levels of tri-methylation of lysine 27 on histone H3 (H3K27me3) and tri-methylation of lysine 4 on histone H3 (H3K4me3) at the VRN1 gene. Analysis of winter wheat transcriptomes before and after vernalization revealed that vernalization influences the expression of several genes, including those involved in leucine catabolism, cysteine biosynthesis, and flavonoid biosynthesis. These findings provide new candidates for further study on the mechanism of vernalization regulation in wheat.

Human umbilical cord mesenchymal stem cells reverse depression in rats induced by chronic unpredictable mild stress combined with lipopolysaccharide.

Inflammation and oxidative stress are considered crucial to the pathogenesis of depression. Rat models of depression can be created by combined treatments of chronic unpredictable mild stress (CUMS) and lipopolysaccharide (LPS). Behaviors associated with depression could be improved by treatment with mesenchymal stem cells (MSCs) owing to immunomodulatory functions of the cells. Therapeutic potentials of the MSCs to reverse pro-inflammatory cytokines, proteins, and metabolites were identified by transcriptomic, proteomic, and metabolomic analysis, respectively. A depression model was established in male SD rats by 2 weeks of CUMS combined with LPS. The models were verified by behavioral tests, namely SPT, OFT, EPM, and qRT-PCR for pro-inflammatory cytokines. Such depressed rats were administered human umbilical cord MSCs (hUC-MSCs) via the tail vein once a week for 2 and 4 weeks. The homing capacity was confirmed by detection of the fluorescent dye on day 7 after the hUC-MSCs were labeled with CM-Dil and administered. The expression of GFAP in astrocytes serves as a biomarker of CNS disorders and IBA1 in microglia serves as a marker of microglia activation were detected by immunohistochemistry at 2 and 4 weeks after final administration of hUC-MSCs. At the same time, transcriptomics of rat hippocampal tissue, proteomic and metabolomic analysis of the serum from the normal, depressed, and treated rats were also compared. Reliable models of rat depression were successfully induced by treatments of CUMS combined with LPS. Rat depression behaviors, pro-inflammatory cytokines, and morphological disorders of the hippocampus associated with depression were reversed in 4 weeks by hUC-MSC treatment. hUC-MSCs could reach the hippocampus CA1 region through the blood circulation on day 7 after administration owing to the disruption of blood brain barrier (BBB) by microglial activation from depression. Differentiations of whole-genome expression, protein, and metabolite profiles between the normal and depression-modeled rats, which were analyzed by transcriptomic, proteomics, and metabolomics, further verified the high association with depression behaviors. Rat depression can be reversed or recovered by treatment with hUC-MSCs.

Whole-Blood Gene Expression Profile After Hypoxic-Ischemic Encephalopathy

Induced hypothermia, the standard treatment for hypoxic-ischemic encephalopathy (HIE) in high-income countries (HICs), is less effective in the low-income populations in South Asia, who have the highest disease burden. To investigate the differences in blood genome expression profiles of neonates with HIE from an HIC vs neonates with HIE from South Asia. This case-control study analyzed data from (1) a prospective observational study involving neonates with moderate or severe HIE who underwent whole-body hypothermia between January 2017 and June 2019 and age-matched term healthy controls in Italy and (2) a randomized clinical trial involving neonates with moderate or severe HIE in India, Sri Lanka, and Bangladesh recruited between August 2015 and February 2019. Data were analyzed between October 2020 and August 2023. Whole-blood RNA that underwent next-generation sequencing. The primary outcomes were whole-blood genome expression profile at birth associated with adverse outcome (death or disability at 18 months) after HIE in the HIC and South Asia cohorts and changes in whole-genome expression profile during the first 72 hours after birth in neonates with HIE and healthy controls from the HIC cohort. Blood samples for RNA extraction were collected before whole-body hypothermia at 4 time points (6, 24, 48, and 72 hours after birth) for the HIC cohort. Only 1 blood sample was drawn within 6 hours after birth for the South Asia cohort. The HIC cohort was composed of 35 neonates (21 females [60.0%]) with a median (IQR) birth weight of 3.3 (3.0-3.6) kg and gestational age of 40.0 (39.0-40.6) weeks. The South Asia cohort consisted of 99 neonates (57 males [57.6%]) with a median (IQR) birth weight of 2.9 (2.7-3.3) kg and gestational age of 39.0 (38.0-40.0) weeks. Healthy controls included 14 neonates (9 females [64.3%]) with a median (IQR) birth weight of 3.4 (3.2-3.7) kg and gestational age of 39.2 (38.9-40.4) weeks. A total of 1793 significant genes in the HIC cohort and 99 significant genes in the South Asia cohort were associated with adverse outcome (false discovery rate <0.05). Only 11 of these genes were in common, and all had opposite direction in fold change. The most significant pathways associated with adverse outcome were downregulation of eukaryotic translation initiation factor 2 signaling in the HIC cohort (z score = -4.56; P < .001) and aldosterone signaling in epithelial cells in the South Asia cohort (z score = null; P < .001). The genome expression profile of neonates with HIE (n = 35) at birth, 24 hours, 48 hours, and 72 hours remained significantly different from that of age-matched healthy controls in the HIC cohort (n = 14). This case-control study found that disease mechanisms underlying HIE were primarily associated with acute hypoxia in the HIC cohort and nonacute hypoxia in the South Asia cohort. This finding might explain the lack of hypothermic neuroprotection.

Unraveling the Secrets of Life: A Comprehensive Overview of Gene Discovery and Gene Mapping

Gene discovery and gene mapping have been key areas of research in genetics and molecular biology for several decades. These processes are fundamental to understanding the genetic basis of numerous diseases and conditions, including cancer, diabetes, and heart disease. Gene discovery involves identifying new genes, while gene mapping involves determining their location within an organism's genome. This essay provides an overview of the methods and technologies used in gene discovery and mapping, including whole-genome sequencing, linkage analysis, association studies, and expression profiling. It also discusses the importance of gene discovery and mapping in advancing our understanding of disease biology and facilitating the development of personalized medicine. Finally, the essay considers the future prospects of these processes, including the potential for new technologies such as single-cell sequencing, CRISPR/Cas9 genome editing, and artificial intelligence to revolutionize the field of genetics research.

Preliminary study on whole genome methylation and transcriptomics in age-related cataracts

DNA methylation plays an important role in the occurrence and development of age-related cataracts (ARC). This study aims to reveal potential epigenetic biomarkers of ARC by detecting modifications to the DNA methylation patterns of genes shown to be related to ARC by transcriptomics. The MethylationEPIC BeadChip (850 K) was used to analyze the DNA methylation levels in ARC patients and unaffected controls, and the Pearson correlation test was used to perform genome-wide integration analysis of DNA methylation and transcriptome data. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were used to perform functional analysis of the whole genome, promoter regions (TSS1500/TSS200), and the associated differentially methylated genes (DMG). Pyrosequencing was used to verify the methylation levels of the selected genes. The results showed that, compared with the control group, a total of 52,705 differentially methylated sites were detected in the ARC group, of which 13,858 were hypermethylated and 38,847 were hypomethylated. GO and KEGG analyses identified functions related to the cell membrane, the calcium signaling pathway, and their possible molecular mechanisms. Then, 57 DMGs with negative promoter methylation correlations were screened by association analysis. Pyrosequencing verified that the ARC group had higher methylation levels of C3 and CCKAR and lower methylation levels of NLRP3, LEFTY1, and GPR35 compared with the control group. In summary, our study reveals the whole-genome DNA methylation patterns and gene expression profiles in ARC, and the molecular markers of methylation identified herein may aid in the prevention, diagnosis, treatment, and prognosis of ARC.

BMC3PM: bioinformatics multidrug combination protocol for personalized precision medicine and its application in cancer treatment

BackgroundIn recent years, drug screening has been one of the most significant challenges in the field of personalized medicine, particularly in cancer treatment. However, several new platforms have been introduced to address this issue, providing reliable solutions for personalized drug validation and safety testing. In this study, we developed a personalized drug combination protocol as the primary input to such platforms.MethodsTo achieve this, we utilized data from whole-genome expression profiles of 6173 breast cancer patients, 312 healthy individuals, and 691 drugs. Our approach involved developing an individual pattern of perturbed gene expression (IPPGE) for each patient, which was used as the basis for drug selection. An algorithm was designed to extract personalized drug combinations by comparing the IPPGE and drug signatures. Additionally, we employed the concept of drug repurposing, searching for new benefits of existing drugs that may regulate the desired genes.ResultsOur study revealed that drug combinations obtained from both specialized and non-specialized cancer medicines were more effective than those extracted from only specialized medicines. Furthermore, we observed that the individual pattern of perturbed gene expression (IPPGE) was unique to each patient, akin to a fingerprint.ConclusionsThe personalized drug combination protocol developed in this study offers a methodological interface between drug repurposing and combination drug therapy in cancer treatment. This protocol enables personalized drug combinations to be extracted from hundreds of drugs and thousands of drug combinations, potentially offering more effective treatment options for cancer patients.

Photosynthetically active radiation is required for seedling growth promotion by volcanic dacitic tuff breccia (Azomite).

A plant's growth and development are shaped by its genome and the capacity to negotiate its environment for access to light, water, and nutrients. There is a vital need to understand the interactions between the plant, its physical environment, and the fertilizers used in agriculture. In this study, a commercially available volcanic ash fertilizer, Azomite®, characterized as dacitic (rhyolitic) tuff breccia, was tested for its effect on promoting early seedling vigor. Early growth and photomorphogenesis processes are well studied in Arabidopsis. Seedling assays under different light conditions were used to dissect the underlying mechanisms involved. These assays are well established and can be translated to agriculturally important crop plants. The volcanic ash fertilizer was tested at different concentrations on seedlings grown on basic media lacking sucrose either in continuous darkness (Dc), continuous Red (Rc), Far-Red (FRc), or White Light (WLc). Micronutrients in the volcanic ash significantly increased seedling growth under Rc and WLc, but not under Dc and FRc, indicating that photosynthetically active radiation was required for the observed growth increase. Furthermore, red-light photoreceptor mutant, phyB-9, lacked the growth response, and higher amount of fertilizer reduced growth in all conditions tested. These data suggest that light triggers the ability of the seedling to utilize micronutrients in volcanic ash in a dose-dependent manner. The methods described here can be used to establish mechanisms of activity of various nutrient inputs and, coupled with whole-genome expression profiling, can lead to better insights into optimizing nutrient field applications to improve crop production.

Genome-wide identification and expression profiling analysis of DIR gene family in Setaria italica.

Dirigent (DIR) proteins play essential roles in regulating plant growth and development, as well as enhancing resistance to abiotic and biotic stresses. However, the whole-genome identification and expression profiling analysis of DIR gene family in millet (Setaria italica (Si)) have not been systematically understood. In this study, we conducted genome-wide identification and expression analysis of the S. italica DIR gene family, including gene structures, conserved domains, evolutionary relationship, chromosomal locations, cis-elements, duplication events, gene collinearity and expression patterns. A total of 38 SiDIR members distributed on nine chromosomes were screened and identified. SiDIR family members in the same group showed higher sequence similarity. The phylogenetic tree divided the SiDIR proteins into six subfamilies: DIR-a, DIR-b/d, DIR-c, DIR-e, DIR-f, and DIR-g. According to the tertiary structure prediction, DIR proteins (like SiDIR7/8/9) themselves may form a trimer to exert function. The result of the syntenic analysis showed that tandem duplication may play the major driving force during the evolution of SiDIRs. RNA-seq data displayed higher expression of 16 SiDIR genes in root tissues, and this implied their potential functions during root development. The results of quantitative real-time PCR (RT-qPCR) assays revealed that SiDIR genes could respond to the stress of CaCl2, CdCl, NaCl, and PEG6000. This research shed light on the functions of SiDIRs in responding to abiotic stress and demonstrated their modulational potential during root development. In addition, the membrane localization of SiDIR7/19/22 was confirmed to be consistent with the forecast. The results above will provide a foundation for further and deeper investigation of DIRs.

Whole-genome DNA methylation and gene expression profiling in the livers of mice with nonalcoholic steatohepatitis

AimsNon-alcoholic fatty liver disease (NAFLD) has emerged as one of the major causes of liver-related morbidity and mortality. It ranges simple steatosis to non-alcoholic steatohepatitis (NASH). Previous studies have shown that epigenetic factors, such as DNA methylation, can contribute to the development and progression of simple steatosis. However, the profiling of whole-genome DNA methylation remains poorly characterized in NASH. Main methodsIn this study, we established a mouse model of diet-induced NASH, by maintaining male mice on a high-fructose-high-cholesterol diet (HFHC), to generate hepatic steatosis, inflammation and injury. We profiled hepatic gene expression by RNA-Sequencing and locus-specific 5-methylcytosine level, using Whole Genome Bisulfite Sequencing (WGBS). Key findingsWe identified >1000 differentially methylated regions in NASH versus control group, indicating that NASH diet could modulate the liver methylome. Furthermore, integrated analysis of methylome and transcriptome identified certain key methylated genes and pathways, which may be involved in steroid metabolism and inflammation response. The liver methylation levels of key genes especially Tgfb, Msn, Iqgap1, Cyba, Fcgr1 decreased, and their consequent increased expression may lead to NASH development. SignificanceWe found that HFHC diet-induced NASH could induces genome-wide differential DNA methylation changes. Thus, we proposed that DNA methylation profiles of genomes may be a useful signature of gene transcription and may play an important role in the development of NASH. We also screened and validated the changes of key genes, which may provide new perspectives for the mechanistic study of NASH in future.

Whole-genome identification and expression profiling of growth-regulating factor (GRF) and GRF-interacting factor (GIF) gene families in Panax ginseng

BackgroundPanax ginseng is a perennial herb and one of the most widely used traditional medicines in China. During its long growth period, it is affected by various environmental factors. Past studies have shown that growth-regulating factors (GRFs) and GRF-interacting factors (GIFs) are involved in regulating plant growth and development, responding to environmental stress, and responding to the induction of exogenous hormones. However, GRF and GIF transcription factors in ginseng have not been reported.ResultsIn this study, 20 GRF gene members of ginseng were systematically identified and found to be distributed on 13 chromosomes. The ginseng GIF gene family has only ten members, which are distributed on ten chromosomes. Phylogenetic analysis divided these PgGRFs into six clades and PgGIFs into two clades. In total, 18 of the 20 PgGRFs and eight of the ten PgGIFs are segmental duplications. Most PgGRF and PgGIF gene promoters contain some hormone- and stress- related cis-regulatory elements. Based on the available public RNA-Seq data, the expression patterns of PgGRF and PgGIF genes were analysed from 14 different tissues. The responses of the PgGRF gene to different hormones (6-BA, ABA, GA3, IAA) and abiotic stresses (cold, heat, drought, and salt) were studied. The expression of the PgGRF gene was significantly upregulated under GA3 induction and three weeks of heat treatment. The expression level of the PgGIF gene changed only slightly after one week of heat treatment.ConclusionsThe results of this study may be helpful for further study of the function of PgGRF and PgGIF genes and lay a foundation for further study of their role in the growth and development of Panax ginseng.

Transcriptomic study of gastrointestinal stromal tumors with liver metastasis.

Introduction: GIST (gastrointestinal stromal tumor) is the most prominent mesenchymal neoplasms of the gastrointestinal tract, and liver is the most common metastasis site for GIST. The molecular mechanism leading to liver metastasis of GIST is currently unclear. Methods: With the goal of revealing the underlying mechanism, we performed whole-genome gene expression profiling on 18 pairs of RNA samples comprised of GIST tissues (with liver metastasis) and corresponding non-tumor tissues. After identifying differentially expressed gene, functional annotation and signal pathway analyses were conducted. GSE13861, datasets that compare GIST (without liver metastasis) with adjacent tissues, served as a comparison. Results: A total of 492 up-regulated genes and 629 down-regulated genes were identified as differentially expressed genes between liver metastasis tissues and non-tumor tissues. We characterized expression patterns of DEGs identified from our cohort and GSE13861 that show signatures of enrichment for functionality. In subsequent gene set enrichment analysis, differentially expressed genes were mainly enriched in Epithelial Mesenchymal Transition in both datasets. 493 genes were overlapped among our whole-genome gene expression profiling results and GSE13861, consisting 188 up-regulated genes and 305 down-regulated genes. By using CytoHubba plugin of Cytoscape, CDH1, CD34, KIT, PROM1, SOX9, FGF2, CD24, ALDH1A1, JAG1 and NES were identified as top ten hub genes in tumorigenesis and liver metastasis of GIST. higher expression levels of FGF2, JAG1, CD34, ALDH1A1 and the lower expression level of CDH1 were respectively associated with unfavorable overall survival. Meanwhile higher expression levels of CD34, FGF2, KIT, JAG1, ALDH1A were correlated with worse disease-free survival. Discussion: The present study may help to provide candidate pathways and targets for treatment of GIST and prevention methods to liver metastasis.

Integrative Methylome and Transcriptome Characterization Identifies SERINC2 as a Tumor-Driven Gene for Papillary Thyroid Carcinoma

Most papillary thyroid carcinomas (PTCs) can be diagnosed preoperatively by routine evaluation, such as thyroid ultrasonography and fine-needle aspiration biopsy. Nevertheless, understanding how to differentiate indolent thyroid tumors from aggressive thyroid cancers remains a challenge, which may cause overtreatment. This study aimed to identify papillary thyroid cancer-specific indicators with whole-genome DNA methylation and gene expression profiles utilizing Infinium Methylation EPIC BeadChip (850k) and RNA arrays. In this paper, we report SERINC2 as a potential tumor-driven indicator in PTC. The up-regulated expression levels of SERINC2 were verified in PTC cell lines via qPCR. Then, cell counting kit 8 (CCK-8), wound healing, and flow cytometric assays were performed to confirm the influence of SERINC2 on proliferation and apoptosis in PTC cell lines after intervention or overexpression. Moreover, the investigation of data from the Cancer Dependency Map (DepMap) provided a potential pathway targeted by SERINC2. The activation of the tryptophan metabolic pathway may reduce the dependency of SERINC2 in thyroid cancers. In conclusion, our results demonstrate the whole-genome DNA methylation and gene expression profiles of papillary thyroid carcinoma, identify SERINC2 as a potential tumor-driven biomarker, and preliminarily verify its function in PTC.

Plant Signals Anticipate the Induction of the Type III Secretion System in Pseudomonas syringae pv. actinidiae, Facilitating Efficient Temperature-Dependent Effector Translocation.

Disease resistance in plants depends on a molecular dialogue with microbes that involves many known chemical effectors, but the time course of the interaction and the influence of the environment are largely unknown. The outcome of host-pathogen interactions is thought to reflect the offensive and defensive capabilities of both players. When plants interact with Pseudomonas syringae, several well-characterized virulence factors contribute to early bacterial pathogenicity, including the type III secretion system (T3SS), which must be activated by signals from the plant and environment to allow the secretion of virulence effectors. The manner in which these signals regulate T3SS activity is still unclear. Here, we strengthen the paradigm of the plant-pathogen molecular dialogue by addressing overlooked details concerning the timing of interactions, specifically the role of plant signals and temperature on the regulation of bacterial virulence during the first few hours of the interaction. Whole-genome expression profiling after 1 h revealed that the perception of plant signals from kiwifruit or tomato extracts anticipated T3SS expression in P. syringae pv. actinidiae compared to apoplast-like conditions, facilitating more efficient effector transport in planta, as revealed by the induction of a temperature-dependent hypersensitive response in the nonhost plant Arabidopsis thaliana Columbia-0 (Col-0). Our results show that in the arms race between plants and bacteria, the temperature-dependent timing of bacterial virulence versus the induction of plant defenses is probably one of the fundamental parameters governing the outcome of the interaction. IMPORTANCE Plant diseases-their occurrence and severity-result from the impact of three factors: the host, the pathogen, and the environmental conditions, interconnected in the disease triangle. Time was further included as a fourth factor accounting for plant disease, leading to a more realistic three-dimensional disease pyramid to represent the evolution of disease over time. However, this representation still considers time only as a parameter determining when and to what extent a disease will occur, at a scale from days to months. Here, we show that time is a factor regulating the arms race between plants and pathogens, at a scale from minutes to hours, and strictly depends on environmental factors. Thus, besides the arms possessed by pathogens and plants per se, the opportunity and the timing of arms mobilization make the difference in determining the outcome of an interaction and thus the occurrence of plant disease.

Genome-wide analysis of MADS-box families and their expressions in flower organs development of pineapple (Ananas comosus (L.) Merr.).

MADS-box genes play crucial roles in plant vegetative and reproductive growth, better development of inflorescences, flower, and fruit. Pineapple is a typical collective fruit, and a comprehensive analysis of the MADS-box gene family in the development of floral organs of pineapple is still lacking. In this study, the whole-genome survey and expression profiling of the MADS-box family in pineapple were introduced. Forty-four AcMADS genes were identified in pineapple, 39 of them were located on 18 chromosomes and five genes were distributed in five scaffolds. Twenty-two AcMADS genes were defined as 15 pairs of segmental duplication events. Most members of the type II subfamily of AcMADS genes had higher expression levels in floral organs compared with type I subfamily, thereby suggesting that AcMADS of type II may play more crucial roles in the development of floral organs of pineapple. Six AcMADS genes have significant tissue-specificity expression, thereby suggesting that they may participate in the formation of one or more floral organs. This study provides valuable insights into the role of MADS-box gene family in the floral organ development of pineapple.

Identification of prognostic biomarkers of invasive ductal carcinoma by an integrated bioinformatics approach

Background: Invasive ductal carcinoma (IDC) is the most common breast cancer worldwide. Nowadays, due to IDC heterogeneity and its high capacity for metastasis, it is necessary to discover novel diagnostic and prognostic biomarkers. Thus, this study aimed to identify new prognostic genes of IDC using an integrated bioinformatics approach. Methods: Using the Gene Expression Omnibus (GEO) database, we downloaded publicly available data of the whole-genome mRNA expression profile from the first three stages of IDC in two expression profiling datasets, GSE29044 and GSE32291; intra-group data repeatability tests were conducted using Pearson’s correlation test, and the differentially expressed genes (DEGs) were identified using the online tool GEO2R, followed by the construction of a protein‑protein interaction network (PPI-net) with the common DEGs identified in the three analyzed stages using the Search Tool for the Retrieval of Interacting Genes (STRING) database and Cytoscape software, from these PPI-net we identify the hub genes (prognostic genes). Results: We found seven genes [WW domain-containing E3 ubiquitin-protein ligase 1 (WWP1), STIP1 homology and U-box containing protein 1 (STUB1), F-box and WD repeat domain containing 7 (FBXW7), kelch like family member 13 (KLHL13), ubiquitin-conjugating enzyme E2 Q1 (UBE2Q1), tripartite motif-containing 11 (TRIM11), and the beta-transducin repeat containing E3 ubiquitin-protein ligase (BTRC)] as potential candidates for IDC prognostic biomarkers, which were mainly enriched in the Ubiquitin-specific protease activity, cytoskeletal protein binding, and ligase activity. The role of these genes in the pathophysiology of IDC is not yet well characterized, representing a way to improve our understanding of the process of tumorigenesis and the underlying molecular events of IDC. Conclusions: Genes identified may lead to the discovery of new prognostic targets and precise therapeutics for IDC.

Ebola virus infection induces a delayed type I IFN response in bystander cells and the shutdown of key liver genes in human iPSC-derived hepatocytes.

SummaryLiver damage and an exacerbated inflammatory response are hallmarks of Ebola virus (EBOV) infection. Little is known about the intrinsic response to infection in human hepatocytes and their contribution to inflammation. Here, we present an induced pluripotent stem cell (iPSC)-derived hepatocyte-like cell (HLC) platform to define the hepato-intrinsic response to EBOV infection. We used this platform to show robust EBOV infection, with characteristic ultrastructural changes and evidence for viral replication. Transcriptomics analysis revealed a delayed response with minimal early transcriptomic changes, followed by a general downregulation of hepatic function and upregulation of interferon signaling, providing a potential mechanism by which hepatocytes participate in disease severity and liver damage. Using RNA-fluorescence in situ hybridization (FISH), we showed that IFNB1 and CXCL10 were mainly expressed in non-infected bystander cells. We did not observe an inflammatory signature during infection. In conclusion, iPSC-HLCs are an immune competent platform to study responses to EBOV infection.

DNA methylation affects freezing tolerance in winter rapeseed by mediating the expression of genes related to JA and CK pathways.

Winter rapeseed is the largest source of edible oil in China and is especially sensitive to low temperature, which causes tremendous agricultural yield reduction and economic losses. It is still unclear how DNA methylation regulates the formation of freezing tolerance in winter rapeseed under freezing stress. Therefore, in this study, the whole-genome DNA methylation map and transcriptome expression profiles of freezing-resistant cultivar NTS57 (NS) under freezing stress were obtained. The genome-wide methylation assay exhibited lower levels of methylation in gene-rich regions. DNA methylation was identified in three genomic sequence contexts including CG, CHG and CHH, of which CG contexts exhibited the highest methylation levels (66.8%), followed by CHG (28.6%) and CHH (9.5%). Higher levels of the methylation were found in upstream 2 k and downstream 2 k of gene regions, whereas lowest levels were in the gene body regions. In addition, 331, 437, and 1720 unique differentially methylated genes (DMGs) were identified in three genomic sequence contexts in 17NS under freezing stress compared to the control. Function enrichment analysis suggested that most of enriched DMGs were involved in plant hormones signal transduction, phenylpropanoid biosynthesis and protein processing pathways. Changes of genes expression in signal transduction pathways for cytokinin (CK) and jasmonic acid (JA) implied their involvement in freezing stress responses. Collectively, these results suggested a critical role of DNA methylation in their transcriptional regulation in winter rapeseed under freezing stress.