scholarly journals Gene Regulatory Divergence Between Locally Adapted Ecotypes in Their Native Habitats

2017 ◽  
Author(s):  
Billie A. Gould ◽  
Yani Chen ◽  
David B. Lowry
Keyword(s):  
Gene Expression ◽  
Differential Expression ◽  
Differentially Expressed Genes ◽  
Differentially Expressed ◽  
Specific Gene ◽  
Transplant Experiment ◽  
Ecological Specialization ◽  
Reciprocal Transplant Experiment ◽  
Chromosome Inversion ◽  
Gene Regulatory

ABSTRACTLocal adaptation is a key driver of ecological specialization and the formation of new species. Despite its importance, the evolution of gene regulatory divergence among locally-adapted populations is poorly understood, especially how that divergence manifests in nature. Here, we evaluate gene expression divergence and allele-specific gene expression responses for locally-adapted coastal perennial and inland annual accessions of the yellow monkeyflower, Mimulus guttatus, in a field reciprocal transplant experiment. Overall, 6765 (73%) of surveyed genes were differentially expressed between coastal and inland habitats, while 7213 (77%) were differentially expressed between the coastal perennial and inland annual accessions. Further, 18% of transcripts had significant genotype x site (GxE) effects. Habitat-specific differential expression was found for 62% of the GxE transcripts (differential expression in one habitat, but not the other), while only 94 (∼5%) GxE transcripts had crossing reaction norms. Cis-regulatory variation was pervasive, affecting 79% (5532) of differentially expressed genes. We detected trans effects for 52% (3611) of differentially expressed genes. Consistent with the supergene hypothesis of chromosome inversion evolution, a locally adaptive inversion was enriched for cis-regulatory divergence. These results provide multiple new insights into the evolution of transcriptome-wide gene regulatory divergence and plasticity among locally adapted populations.

scholarly journals Gene Expression Profiling of Sorted Peripheral Blood Cells Using Microarray and Next Generation Sequencing Reveals Distinct Molecular Signatures in the Polymorphonuclear and Mononuclear Cells of Patients with Polycythemia Vera and Primary Myelofibrosis

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5201-5201
Author(s):  
Chieh Lee Wong ◽  
Baoshan Ma ◽  
Gareth Gerrard ◽  
Martyna Adamowicz-Brice ◽  
Zainul Abidin Norziha ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Gene Expression Profiling ◽  
Differential Expression ◽  
Differentially Expressed Genes ◽  
Expression Profiling ◽  
Differentially Expressed ◽  
Cell Type ◽  
Cell Type Specific ◽  
Generation Sequencing

Abstract Background The past decade has witnessed a significant progress in the understanding of the molecular pathogenesis of myeloproliferative neoplasms (MPN). A large number of genes have now been implicated in the pathogenesis of MPN but their relative importance, the mechanisms by which they cause different cell types to predominate and their implications for prognosis remain unknown. We hypothesized that there are other genes which may contribute to the pathogenesis of the different disease subtypes detectable only by cell-type specific analysis. Aim The aim of this study was to perform gene expression profiling on different cell types from patients with MPN in order to identify novel variants and driver mutations, to elucidate the pathogenesis and to identify predictors of survival in patients with MPN in a multiracial country. Methods We performed gene expression profiling on normal controls (NC) and patients with MPN from 3 different races (Malay, Chinese and Indian) in Malaysia who were diagnosed with essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF) according to the 2008 WHO diagnostic criteria for MPN. Two cohorts of patients, the patient and validation cohorts, from 3 tertiary-level hospitals were recruited prospectively over 3 years and informed consents were obtained. Peripheral blood samples were taken and sorted into polymorphonuclear cells (PMNs), mononuclear cells (MNCs) and T cells. RNA was extracted from each cell population. Gene expression profiling was performed using the Illumina HumanHT-12 Expression Beadchip for microarray and the Illumina Nextera XT DNA Sample Preparation Kit for next generation sequencing on the patient and validation cohorts respectively. Results Twenty-eight patients (10 ET, 11 PV and 7 PMF) and 11 NC were recruited into the patient cohort. Twelve patients (4 ET, 4 PV and 4 PMF) and 4 NC were recruited into the validation cohort. Gene expression levels for each cell type in each disease were compared with NC. In the patient cohort, the number of differentially expressed genes in ET, PV and PMF was 0, 141 and 15 respectively for PMNs (p < 0.05 after multiple testing correction) and 5, 170 and 562 respectively for MNCs (p < 0.05). No differentially expressed genes were identified for T cells in any of the three disease groups. RNA-seq analysis of samples from the validation cohort was used to corroborate these findings. After combination, we were able to confirm differential expression of 0, 14 and 7 genes in ET, PV and PMF respectively for PMNs (p < 0.05) and 51 genes in only PMF for MNCs (p < 0.05). The validated differentially expressed genes for PMNs and MNCs were mutually exclusive except for one gene. The differentially expressed genes in PV and PMF for PMNs were involved in cellular processes and metabolic pathways whereas the differentially expressed genes for PMF in MNCs were involved in regulation of cytoskeleton, focal adhesion and cell signaling pathways. Conclusion This is the first study to use microarray and next generation sequencing techniques to compare cell type-specific expression of genes between different subtypes of MPN. The lack of differential expression in T cells validates the techniques used and indicates that they are not part of the neoplastic clone. Differential expression of genes for MNCs was seen only in PMF which may be related to their more severe phenotype. Interestingly, there were fewer differentially expressed genes in PMF compared to PV for PMNs. The lack of differential expression in ET may either reflect the relatively milder phenotype of the disease or that differential expression is limited to megakaryocytes-platelets which were not studied. The lists of mutually exclusive cell type-specific differentially expressed genes for PMNs and MNCs provide further insight into the pathogenesis of MPN and into the differences between its different forms. The identified genes also indicate further routes for investigation of pathogenesis and possible disease-specific targets for therapy. Disclosures Aitman: Illumina: Honoraria.

scholarly journals Bioinformatics Study on the Response of Human Endothelial Cells to Different Strains of Staphylococcus Aureus

2020 ◽  
Author(s):  
Tian-ao Xie ◽  
Ke-ying Fang ◽  
Wen-chao Cao ◽  
Jie Lv ◽  
Jia-xin Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Staphylococcus Aureus ◽  
Endothelial Cells ◽  
Differentially Expressed Genes ◽  
Expression Patterns ◽  
Differentially Expressed ◽  
Specific Gene ◽  
Human Endothelial Cells ◽  
Different Strains ◽  
Differential Genes

Abstract BackgroundStaphylococcus aureus-induced bacteremia has an impact on human health due to its high mortality rate of 20–30%. To better study the invasion process of staphylococcus aureus, we conducted a study in human endothelial cells to try to find a link between the infection process and bacteremia at the molecular level.MethodsIn this study, the datasets GSE13736, GSE82036 were analyzed using R software to identify differentially expressed genes. Only the infection samples of four different strains had differential gene expression compared to the control samples. Then the GO analysis and KEGG analysis were conducted to construct a protein-protein interaction (PPI) network which shows the interaction and influence relationship between these differential genes. Finally, the central gene of the selected CytoHubba plug-in was verified using GraphPad Prism 8.ResultsThere were 421 differential genes in the Strain 6850, including 64 up-regulated and 357 down-regulated; There were 319 differential genes in the Strain 8325-4, including 14 up-regulated and 305 down-regulated. There were 90 differential genes in the Strain K70058396, including 12 up-regulated and 78 down-regulated. There were 876 differential genes in the Strain K1801/10, accompanied by 261 up-regulated and 615 down-regulated. An analysis of GO and KEGG revealed that these differentially expressed genes were significantly enriched in pathways associated with immune response and cytokines; Verification of the hub gene can provide a molecular basis for studying the relationship between invasive endothelial infection and bacteremia.ConclusionsWe found specific gene expression patterns in endothelial cells in response to infection with Strain K70058396, and these central genes and their expression products (RSAD2, DDX58, IFITT3, and IFIH1) play a key role in this process of infection.

The NOD/SCID Xenograft Model Provides Clinically-Relevant Insights Into Glucocorticoid-Induced Gene Expression In Childhood B-Cell Precursor Acute Lymphoblastic Leukemia (ALL)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2493-2493
Author(s):  
Vivek A Bhadri ◽  
Mark J Cowley ◽  
Warren Kaplan ◽  
Richard B Lock
Keyword(s):  
Gene Expression ◽  
Acute Lymphoblastic Leukemia ◽  
Mouse Model ◽  
B Cell ◽  
Differential Expression ◽  
Differentially Expressed Genes ◽  
Lymphoblastic Leukemia ◽  
Xenograft Model ◽  
Differentially Expressed ◽  
Cell Precursor

Abstract Abstract 2493 Introduction. Glucocorticoids (GC) such as prednisolone (Pred) and dexamethasone (Dex) are critical drugs in multi-agent chemotherapy protocols used to treat acute lymphoblastic leukemia (ALL). The NOD/SCID ALL xenograft mouse model is a clinically relevant model in which the mice develop a systemic leukemia which retains the fundamental biological characteristics of the original disease. Here we report the results of a study evaluating the NOD/SCID xenograft model to investigate GC-induced gene expression. Methods. Cells from a GC-sensitive xenograft derived from a child with B-cell precursor ALL were inoculated into NOD/SCID mice. Engraftment, defined as the proportion of human vs mouse CD45+ cells in the peripheral blood, was monitored by serial weekly tail-vein sampling. When engraftment levels reached >50%, the mice were randomised and treated with either dexamethasone 15 mg/kg or vehicle control by intraperitoneal injection, and harvested at 0, 8, 24 or 48 h thereafter. The 48 hour groups received a second dose of vehicle or Dex at 24 hours. At the defined timepoints, the mice were euthanized and lymphoblasts harvested from the spleen. RNA was extracted, amplified and hybridised onto Illumina WG-6 V3 chips. The data was pre-processed using variance-stabilisation transformation, and quantile normalisation. Differential expression was determined using limma by comparing all treated groups to time 0, with the positive False Discovery Rate correction for multiple testing. Hierarchical clustering was used to compare groups to each other. The stability of results when reducing the number of replicates was assessed using the Recovery Score method. Functional analysis was performed using gene set enrichment analysis (GSEA) and comparison to publicly available microarray data using parametric GSEA. Results. The 8 hour Dex-treated timepoint had the most number of significantly differentially expressed genes (see Table), with fewer observed at the 24 and 48 hour Dex-treated timepoints. There was minimal significant differential gene expression across the time-matched controls. At the 8 hour timepoint, ZBTB16, a known GC-induced gene, was the most significantly upregulated gene. Other significantly differentially expressed genes included TSC22D3 and SOCS1, both downstream targets of the glucocorticoid receptor (upregulated), and BCL-2 and C-MYC (downregulated). GSEA at 8 hours revealed a significant upregulation of catabolic pathways and downregulation of pathways associated with cell proliferation, particularly C-MYC. GSEA at 24 hours revealed enrichment of pathways associated with NF-kB. Replicate analysis revealed that at the 8 hour Dex treated timepoint, a dataset with high signal and differential expression, using data from 3 replicates instead of 4 resulted in excellent recovery scores of >0.9. However at other timepoints with less signal very poor recovery scores were obtained using 3 replicates. We compared our data to publicly available datasets of GC-induced genes in ALL (Schmidt et al, Blood 2006; Rainer et al, Leukemia 2009) using parametric GSEA, which revealed that the 8 hour gene expression data obtained from the NOD/SCID xenograft model clustered with data from primary patient samples (Schmidt) rather than the cell line data (Rainer). The 24 and 48 hour datasets clustered separately from all other datasets by this method, reflecting fewer and predominantly downregulated gene expression at these timepoints. Conclusions: The NOD/SCID xenograft mouse model provides a reproducible experimental model system in which to investigate clinically-relevant mechanisms of GC-induced gene regulation in ALL; the 8 hour timepoint provides the highest number of significantly differentially expressed genes; time-matched controls are redundant and excellent recovery scores can be obtained with 3 replicates. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Novel Significant Stage-Specific Differentially Expressed Genes in Liver Hepatocellular Carcinoma

2018 ◽  
Author(s):  
Arjun Sarathi ◽  
Ashok Palaniappan
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Differentially Expressed Genes ◽  
Stage Iv ◽  
Differentially Expressed ◽  
Driver Gene ◽  
P Value ◽  
Specific Gene ◽  
Multiple Sources ◽  
Two Stage

ABSTRACTLiver cancer is among the top deadly cancers worldwide with a very poor prognosis, and the liver is a particularly vulnerable site for metastasis of other cancers. In this study, we developed a novel computational framework for the stage-specific analysis of hepatocellular carcinoma initiation and progression. Using publicly available clinical and RNA-Seq data of cancer samples and controls, we annotated the gene expression matrix with sample stages. We performed a linear modelling analysis of gene expression across all stages and found significant genome-wide changes in gene expression in cancer samples relative to control. Using a contrast against the control, we were able to identify differentially expressed genes (log fold change >2) that were significant at an adjusted p-value < 10E-3. In order to identify genes that were specific to each stage without confounding differential expression in other stages, we developed a full set of pairwise stage contrasts and enforced a p-value threshold (<0.05) for each such contrast. Genes were specific for a stage if they passed all the significance filters for that stage. Our analysis yielded two stage-I specific genes (CA9, WNT7B), two stage-II specific genes (APOBEC3B, FAM186A), ten stage-III specific genes including DLG5, PARI and GNMT, and ten stage-IV specific genes including GABRD, PGAM2 and PECAM1. Of these, only APOBEC3B is an established cancer driver gene. DLG5 was found to be tumor-promoting contrary to the cancer literature on this gene. Further, GABRD, well studied in literature on other cancers, emerged as a stage-IV specific gene. Our findings could be validated using multiple sources of omics data as well as experimentally. The biomarkers identified herein could potentially underpin diagnosis as well as pinpoint drug targets.

B-Cell Chronic Lymphocytic Leukemia Cells Exposed to the Non-Genotoxic p53 Activator Nutlin-3 Are Characterized by a Specific Gene Expression Signature.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4374-4374
Author(s):  
Michele Dal-Bo ◽  
Paola Secchiero ◽  
Massimo Degan ◽  
Riccardo Bomben ◽  
Dania Benedetti ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Differentially Expressed Genes ◽  
Chemotherapeutic Agents ◽  
Lymphocytic Leukemia ◽  
Differentially Expressed ◽  
Specific Gene ◽  
P53 Mutations ◽  
Cell Chronic Lymphocytic Leukemia

Abstract Abstract 4374 Introduction p53 plays a key role in determining the clinical features of B cell chronic lymphocytic leukemia (CLL). Disruption of p53 by point mutations, deletion at 17p13, or both, occurs in a fraction of cases at diagnosis and predicts poor survival and chemorefractoriness. In cells with functional p53, p53 activity is inhibited through interaction with MDM2. In fact, p53 can be activated upon exposure of cells to inhibitors of p53/MDM2 interaction, like Nutlins. Exposure of CLL cells to Nutlin-3 is effective in raising the levels of p53 protein with subsequent induction of cell cycle arrest and/or apoptosis, independently of the most relevant prognostic markers. The aim of the present study was to analyze the gene expression profile (GEP) induced by Nutlin-3 exposure in primary CLL cells from p53wt and p53del/mut cases. Patients and methods purified cells from 24 PB CLL samples, all characterized for IGHV mutational status, CD38 and ZAP-70 and p53 mutations (16 p53wt CLL, 8 p53del/mut CLL of which 6 with del17p13 and p53 mutations, 1 with del17p13 alone, and 1 with p53 mutations alone), were exposed to 10 mM Nutlin-3 for 24 hours. GEP was performed using a dual labelling strategy; the differential expression of the below reported genes were validated by quantitative real-time PCR. Results i) signature of Nutlin-3 exposure in p53wt CLL: 144 differentially expressed genes (143 up-regulated, 1 down-regulated) were correlated with response to Nutlin-3. Among the over-expressed genes, several genes were related to apoptosis (e.g. BAX, BBC3, E124, IKIP, FAS, LRDD, FLJ11259, TRIAP1, GADD45, TP53INP1, ISG20L1, ZMAT3, TNFRS10C, TNFRSF10B/TRAIL-R2), while other genes (e.g. MDM2, CDKN1A, PCNA) were up-regulated by Nutlin-3 as a part of a negative feed-back mechanism. Of note, this signature was not shared by 3/16 p53wt cases (identified as “non-responder” p53wt CLL) and 7/8 p53del/mut cases (identified as “non-responder” p53del/mut CLL); consistently, cells from these cases were also significantly resistant to the in-vitro cytotoxic effects of Nutlin-3; ii) signature of Nutlin-3 “non-responder” p53wt CLL: by comparing the constitutive GEP of 13 “responder” versus 3 “non-responder” p53wt CLL, we obtained 278 differentially expressed genes, 149 up-regulated and 129 down-regulated in “non-responder” p53wt CLL. Among up-regulated genes, we focused on MDM4/MDMX, a gene whose product was known to have an inhibitor activity of p53-dependent transcription and to form Nutlin-3 resistant complexes with p53. Among down-regulated genes, validations were made for BIRC4BP, whose product is known to act as an antagonist of the anti-apoptotic protein XIAP; iii) signature of Nutlin-3 “non-responder” p53del/mut CLL: by comparing the constitutive GEP of 13 “responder” versus 7 “non-responder” p53del/mut cases, we obtained 72 differentially expressed genes, 26 up-regulated and 46 down-regulated (31/46 located at the 17p segment) in “non-responder” p53del/mut CLL. Validations were made for several genes whose products display pro-apoptotic activities (e.g. PSMB6, RPL26 and ZBTB4, located at 17p segment, and GNAZ located at chromosome 22) among down-regulated genes, and ARHGDIA, whose gene product displays anti-apoptotic activities and mediates cellular resistance to chemotherapeutic agents, among up-regulated genes. Notably, CLL cells (n=43) displayed constitutively higher levels of MDM4/MDMX (p<0.0001) and ARHGDIA (p=0.0002) transcripts than purified normal B cells (n=15), irrespectively to the major biologic prognosticators. Conclusions specific gene-sets and GEP were documented to be associated with response or resistance to Nutlin-3 exposure in p53wt or p53del/mut CLL. These findings may help to identify novel molecular targets for CLL therapy. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Tissue and Temperature-Specific RNA-Seq Analysis Reveals Genomic Versatility and Adaptive Potential in Wild Sea Turtle Hatchlings (Caretta caretta)

Animals ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 3013
Author(s):  
Julie C. Chow ◽  
Nia Kyritsis ◽  
Micah Mills ◽  
Matthew H. Godfrey ◽  
Craig A. Harms ◽  
...  
Keyword(s):  
Gene Expression ◽  
Differentially Expressed Genes ◽  
Sexual Development ◽  
Caretta Caretta ◽  
Sea Turtle ◽  
Differentially Expressed ◽  
Specific Gene ◽  
Rna Seq ◽  
Loggerhead Sea Turtle ◽  
Male And Female

Background: Digital transcriptomics is rapidly emerging as a powerful new technology for modelling the environmental dynamics of the adaptive landscape in diverse lineages. This is particularly valuable in taxa such as turtles and tortoises (order Testudines) which contain a large fraction of endangered species at risk due to anthropogenic impacts on the environment, including pollution, overharvest, habitat degradation, and climate change. Sea turtles (family Cheloniidae) in particular invite a genomics-enabled approach to investigating their remarkable portfolio of adaptive evolution. The sex of the endangered loggerhead sea turtle (Caretta caretta) is subject to temperature-dependent sex determination (TSD), a mechanism by which exposure to temperatures during embryonic development irreversibly determines sex. Higher temperatures produce mainly female turtles and lower temperatures produce mainly male turtles. Incubation temperature can have long term effects on the immunity, migratory ability, and ultimately longevity of hatchlings. We perform RNA-seq differential expression analysis to investigate tissue- and temperature-specific gene expression within brain (n = 7) and gonadal (n = 4) tissue of male and female loggerhead hatchlings. Results: We assemble tissue- and temperature-specific transcriptomes and identify differentially expressed genes relevant to sexual development and life history traits of broad adaptive interest to turtles and other amniotic species. We summarize interactions among differentially expressed genes by producing network visualizations, and highlight shared biological pathways related to migration, immunity, and longevity reported in the avian and reptile literature. Conclusions: The measurement of tissue- and temperature-specific global gene expression of an endangered, flagship species such as the loggerhead sea turtle (Caretta caretta) reveals the genomic basis for potential resiliency and is crucial to future management and conservation strategies with attention to changing climates. Brain and gonadal tissue collected from experimentally reared loggerhead male and female hatchlings comprise an exceedingly rare dataset that permits the identification of genes enriched in functions related to sexual development, immunity, longevity, and migratory behavior and will serve as a large, new genomic resource for the investigation of genotype–phenotype relationships in amniotes.

Abstract 1726: Genome-Wide Cell-Specific Gene Expression Analysis Identifies the Involvement of the Adipocytokine Signalling Pathway in Atherosclerotic Plaque Rupture

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Kelvin Lee ◽  
Tuomo Polvikoski ◽  
Daniel Birchall ◽  
Mauro Santibanez-Koref ◽  
Alexander D Mendelow ◽  
...  
Keyword(s):  
Gene Expression ◽  
Differentially Expressed Genes ◽  
Molecular Mechanisms ◽  
Plaque Rupture ◽  
Pearson Correlation ◽  
Signalling Pathway ◽  
Differentially Expressed ◽  
Immunocytochemical Staining ◽  
Specific Gene ◽  
Genome Wide

The molecular mechanisms leading to plaque rupture are poorly understood. Genome-wide gene expression studies may reveal novel causal molecular pathways. METHODS: Snap-frozen human atherosclerotic plaques removed at carotid endarterectomy were designated as stable or ruptured using stringent clinical, radiological and histopathological criteria. Accurate gene expression profiling of macrophages in 5 ruptured and 6 stable plaques was conducted by employing Laser Micro-Dissection to specifically isolate this cell type from the plaques. High quality RNA was amplified and hybridised to the genome-wide Affymetrix U133plus2 microarray. RESULTS: Exploratory clustering by Principal Components Analysis showed the data to cluster into 2 distinct groups- stable and ruptured. We identified 889 statistically significant differentially expressed genes between the two groups (Fig.1 ). Genes involved in lipid processing, signalling, apoptosis, immune response and extracellular matrix were found to play a role in plaque rupture. Pathway analysis identified the Adipocytokine Signalling Pathway to be the most significantly represented cell signalling pathway (p<0.0006). The microarray findings were technically validated by real-time qPCR (Pearson Correlation R=0.94) and biologically cross-validated on a larger number of samples successfully (n=25). Immunocytochemical staining confirmed the differential Leptin expression in macrophages of ruptured and stable plaques. CONCLUSION: The involvement of Leptin and the Adipocytokine Signalling Pathway in macrophages in plaque rupture has been implicated here for the first time and may be a potential therapeutic target. Figure 1. Heatmap of 889 statistically significant differentially expressed genes (red for high expression, green for low expression) with the top 20 most highly expressed genes in ruptured and stable groups listed.

scholarly journals Identification and validation of hub genes of synovial tissue for patients with osteoarthritis and rheumatoid arthritis

2021 ◽  
Author(s):  
Yanzhi Ge ◽  
Zuxiang Chen ◽  
Yanbin Fu ◽  
Li Zhou ◽  
Haipeng Xu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Differentially Expressed Genes ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Interaction Network ◽  
Differentially Expressed ◽  
Specific Gene ◽  
Hub Genes

Abstract Osteoarthritis (OA) and rheumatoid arthritis (RA) were two major joint diseases with partially common phenotypes and genotypes. This study aimed to determine the mechanistic similarities and differences between osteoarthritis and rheumatoid arthritis by analyzing the differentially expressed genes and signaling pathways. Microarray data of osteoarthritis and rheumatoid arthritis were obtained from the Gene Expression Omnibus. By integrating multiple gene data sets, specific differentially expressed genes (DEGs) were identified in synovial membrane samples from patients and healthy donations. Then, the Gene ontology significant functions annotation, Kyoto Encyclopedia of Genes and Genomes pathways and protein-protein interaction network analysis were conducted. Moreover, CIBERSORT was used to further distinguish OA and RA in immune infiltration. Finally, animal experimentation was conducted and the establishment of model, which was verified using PCR in the mouse. As an overlapping process, we identified 1116 DEGs between OA and RA. It was indicated that specific gene signatures differed significantly between OA and RA connected with the distinct pathways. Of identified DEGs, 9 immune cell types among 22 were identified to distinguish from each other. The qRT-PCR result showed that the eight-tenths expression levels of the hub genes were significantly increased in OA samples (P < 0.05). This large-scale gene expression study provided new insights for disease-associated genes and molecular mechanisms as well as their associated function in osteoarthritis and rheumatoid arthritis, which simultaneously offer a new direction for biomarker development and the distinguishment of gene-level mechanisms between osteoarthritis and rheumatoid arthritis.

scholarly journals The Molecular Basis of Kale Domestication: Transcriptional Profiling of Developing Leaves Provides New Insights Into the Evolution of a Brassica oleracea Vegetative Morphotype

2021 ◽  
Vol 12 ◽  
Author(s):  
Tatiana Arias ◽  
Chad E. Niederhuth ◽  
Paula McSteen ◽  
J. Chris Pires
Keyword(s):  
Gene Expression ◽  
Brassica Oleracea ◽  
Candidate Genes ◽  
Differentially Expressed Genes ◽  
Leaf Morphology ◽  
Plant Architecture ◽  
Differentially Expressed ◽  
Specific Gene ◽  
Domestication Syndrome ◽  
Cole Crop

Morphotypes ofBrassica oleraceaare the result of a dynamic interaction between genes that regulate the transition between vegetative and reproductive stages and those that regulate leaf morphology and plant architecture. In kales, ornate leaves, extended vegetative phase, and nutritional quality are some of the characters potentially selected by humans during domestication. We used a combination of developmental studies and transcriptomics to understand the vegetative domestication syndrome of kale. To identify candidate genes that are responsible for the evolution of domestic kale, we searched for transcriptome-wide differences among three vegetativeB. oleraceamorphotypes. RNA-seq experiments were used to understand the global pattern of expressed genes during a mixture of stages at one time in kale, cabbage, and the rapid cycling kale line TO1000. We identified gene expression patterns that differ among morphotypes and estimate the contribution of morphotype-specific gene expression that sets kale apart (3958 differentially expressed genes). Differentially expressed genes that regulate the vegetative to reproductive transition were abundant in all morphotypes. Genes involved in leaf morphology, plant architecture, defense, and nutrition were differentially expressed in kale. This allowed us to identify a set of candidate genes we suggest may be important in the kale domestication syndrome. Understanding candidate genes responsible for kale domestication is of importance to ultimately improve Cole crop production.

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