Apomixis-related genes identified from a coexpression network inPaspalum notatum, a Neotropical grass

AbstractApomixis is a highly desirable trait in modern agriculture, due to the maintenance of characteristics of the mother plant in the progeny. However, incorporating it into breeding programs requires a deeper knowledge of its regulatory mechanisms.Paspalum notatumis considered a good model for such studies because it exhibits both sexual and apomictic cytotypes, facilitating the performance of comparative approaches. Therefore, we used comparative transcriptomics between contrastingP. notatumcytotypes to identify novel candidate genes involved in the regulation of the expression of this phenotype. We assembled and characterized a transcriptome from leaf and inflorescence from apomictic tetraploids and sexual diploids/tetraploids ofP. notatumaccessions, and then assembled a coexpression network based on pairwise correlation between transcripts expression profiles. We identified genes exclusively expressed in each cytotype and differentially expressed genes between pairs of cytotypes. Gene ontology enrichment analyses were performed for the interpretation of data. Wede novoassembled 114,306 of reference transcripts. 536 novel candidate genes for the control of apomixis were detected through statistical analyses of expression data, contains in this set, the interactions among genes potentially linked to the apomixis-controlling region, differentially expressed, several genes also already reported in the literature and their neighbors transcriptionally related in the coexpression network. The reference transcriptome obtained in this study represents a robust set of expression data forP. notatum. Additionally, novel candidate genes identified in this work represent a valuable resource for future grass breeding programs.Author SummaryClonal mode of reproduction by seeds is termed apomixis, which results from the failure of gamete formation (meiosis) and fertilization in the sexual female reproductive pathway. The manipulation of seeds production genetically identical to the mother plant bears great promise for agricultural applications, however clarification regarding gene interactions involved in reproductive process is needed.Paspalumis considered a model genus for the analysis of apomixis mechanisms. Here, we describe an overall analysis of the expression profiles ofPaspalum notatumtranscripts in response to changes in reproductive mode (sexual to apomictic), which allowed us to identify several candidate apomixis genes. Among these, we found genes potentially associated with the apomixis control region, in addition to genes already described in the literature forPaspalum, which highlights the representativeness of assembled transcriptome. For the first time in the literature, we explored the main biological processes involved in controlling the expression of apomictic reproduction based on co-regulatory networks of candidate apomixis genes.

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Association Between Gene Expression Profiles and Commonly Mutated Genes In The Hematopoietic Stem Cells Of Patients With Myelodysplastic Syndromes

Blood ◽

10.1182/blood.v122.21.2779.2779 ◽

2013 ◽

Vol 122 (21) ◽

pp. 2779-2779 ◽

Cited By ~ 1

Author(s):

Andrea Pellagatti ◽

Moritz Gerstung ◽

Elli Papaemmanuil ◽

Luca Malcovati ◽

Aristoteles Giagounidis ◽

...

Keyword(s):

Gene Expression ◽

Differentially Expressed Genes ◽

Gene Expression Data ◽

Expression Profiles ◽

Gene Mutations ◽

Gene Expression Profiles ◽

Differentially Expressed ◽

Expression Data ◽

Common Gene ◽

Mutational Status

Abstract A particular profile of gene expression can reflect an underlying molecular abnormality in malignancy. Distinct gene expression profiles and deregulated gene pathways can be driven by specific gene mutations and may shed light on the biology of the disease and lead to the identification of new therapeutic targets. We selected 143 cases from our large-scale gene expression profiling (GEP) dataset on bone marrow CD34+ cells from patients with myelodysplastic syndromes (MDS), for which matching genotyping data were obtained using next-generation sequencing of a comprehensive list of 111 genes involved in myeloid malignancies (including the spliceosomal genes SF3B1, SRSF2, U2AF1 and ZRSR2, as well as TET2, ASXL1and many other). The GEP data were then correlated with the mutational status to identify significantly differentially expressed genes associated with each of the most common gene mutations found in MDS. The expression levels of the mutated genes analyzed were generally lower in patients carrying a mutation than in patients wild-type for that gene (e.g. SF3B1, ASXL1 and TP53), with the exception of RUNX1 for which patients carrying a mutation showed higher expression levels than patients without mutation. Principal components analysis showed that the main directions of gene expression changes (principal components) tend to coincide with some of the common gene mutations, including SF3B1, SRSF2 and TP53. SF3B1 and STAG2 were the mutated genes showing the highest number of associated significantly differentially expressed genes, including ABCB7 as differentially expressed in association with SF3B1 mutation and SULT2A1 in association with STAG2 mutation. We found distinct differentially expressed genes associated with the four most common splicing gene mutations (SF3B1, SRSF2, U2AF1 and ZRSR2) in MDS, suggesting that different phenotypes associated with these mutations may be driven by different effects on gene expression and that the target gene may be different. We have also evaluated the prognostic impact of the GEP data in comparison with that of the genotype data and importantly we have found a larger contribution of gene expression data in predicting progression free survival compared to mutation-based multivariate survival models. In summary, this analysis correlating gene expression data with genotype data has revealed that the mutational status shapes the gene expression landscape. We have identified deregulated genes associated with the most common gene mutations in MDS and found that the prognostic power of gene expression data is greater than the prognostic power provided by mutation data. AP and MG contributed equally to this work. JB and PJC are co-senior authors. Disclosures: No relevant conflicts of interest to declare.

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Construction of potential periodontitis-related miRNA-mRNA regulatory network

10.21203/rs.3.rs-109574/v1 ◽

2020 ◽

Author(s):

Zheng Zhang ◽

Youli Zheng ◽

Xiaowei Bian ◽

Mingguang Jin

Keyword(s):

Candidate Genes ◽

Regulatory Network ◽

Molecular Mechanisms ◽

Target Genes ◽

Expression Profiles ◽

Multivariate Logistic Regression Analysis ◽

Gene Expression Profiles ◽

Mirna Expression Profile ◽

Differentially Expressed ◽

B Cell Differentiation

Abstract Background MicroRNAs (miRNAs) are found to be involved in the pathogenesis of periodontitis, a major cause of tooth loss in adults. However, a comprehensive miRNA-mRNA regulatory network has still not been established. Methods One miRNA expression profile and 2 gene expression profiles were downloaded from the GEO database and analyzed using GEO2R. Candidate genes commonly appeared in differentially expressed mRNAs (DE-mRNAs) and target genes of differentially expressed miRNAs (DE-miRNAs) were selected for functional and pathway enrichment analyses using Enrichr database. Multivariate Logistic regression analysis was used to screen independent variables among candidate genes. The diagnostic values of screened genes were determined by the area under the receiver operating characteristic (ROC) curve (AUC). Results A total of 5 DE-miRNAs (4 upregulated and 1 downregulated) and 11 candidate genes (3 upregulated and 8 downregulated) were screened. After the construction of miRNA-mRNA regulatory network, 12 miRNA-mRNA pairs were identified. In the network, the upregulated genes were significantly enriched in cellular triglyceride homeostasis and positive regulation of B cell differentiation, whereas the downregulated genes were enriched in vesicle organization, negative regulation of lymphocyte and leukocyte migration. EPCAM and RAB30 were screened as risk factors of periodontitis. The combined AUC of these 2 genes was 0.896 (GSE10334) and 0.916 (GSE16134). Conclusion In this study, we established a potential periodontitis-related miRNA-mRNA regulatory network, which brings new insights into the molecular mechanisms and provides key clues in seeking novel therapeutic targets for periodontitis. In the future, more experiments need to be carried out to validate our current findings.

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Network-based analysis of differentially expressed genes in cerebrospinal fluid (CSF) and blood reveals new candidate genes for multiple sclerosis

PeerJ ◽

10.7717/peerj.2775 ◽

2016 ◽

Vol 4 ◽

pp. e2775 ◽

Cited By ~ 15

Author(s):

Nahid Safari-Alighiarloo ◽

Mostafa Rezaei-Tavirani ◽

Mohammad Taghizadeh ◽

Seyyed Mohammad Tabatabaei ◽

Saeed Namaki

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Candidate Genes ◽

Differentially Expressed Genes ◽

Expression Profiles ◽

Biological Pathways ◽

Differentially Expressed ◽

Potential Candidate ◽

Functional Modules ◽

Ppi Networks

BackgroundThe involvement of multiple genes and missing heritability, which are dominant in complex diseases such as multiple sclerosis (MS), entail using network biology to better elucidate their molecular basis and genetic factors. We therefore aimed to integrate interactome (protein–protein interaction (PPI)) and transcriptomes data to construct and analyze PPI networks for MS disease.MethodsGene expression profiles in paired cerebrospinal fluid (CSF) and peripheral blood mononuclear cells (PBMCs) samples from MS patients, sampled in relapse or remission and controls, were analyzed. Differentially expressed genes which determined only in CSF (MSvs.control) and PBMCs (relapsevs.remission) separately integrated with PPI data to construct the Query-Query PPI (QQPPI) networks. The networks were further analyzed to investigate more central genes, functional modules and complexes involved in MS progression.ResultsThe networks were analyzed and high centrality genes were identified. Exploration of functional modules and complexes showed that the majority of high centrality genes incorporated in biological pathways driving MS pathogenesis. Proteasome and spliceosome were also noticeable in enriched pathways in PBMCs (relapsevs.remission) which were identified by both modularity and clique analyses. Finally, STK4, RB1, CDKN1A, CDK1, RAC1, EZH2, SDCBP genes in CSF (MSvs.control) and CDC37, MAP3K3, MYC genes in PBMCs (relapsevs.remission) were identified as potential candidate genes for MS, which were the more central genes involved in biological pathways.DiscussionThis study showed that network-based analysis could explicate the complex interplay between biological processes underlying MS. Furthermore, an experimental validation of candidate genes can lead to identification of potential therapeutic targets.

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Transcriptomic analysis of temporal shifts in berry development between two grapevine cultivars of the Pinot family reveals potential ripening-regulative genes

10.1101/2021.03.18.436038 ◽

2021 ◽

Author(s):

Jens Theine ◽

Daniela Holtgräwe ◽

Katja Herzog ◽

Florian Schwander ◽

Anna Kicherer ◽

...

Keyword(s):

Gene Expression ◽

Candidate Genes ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Regulatory Genes ◽

Pinot Noir ◽

Differentially Expressed ◽

Berry Development ◽

Ripening Time ◽

Berry Ripening

Background Grapevine cultivars of the Pinot family represent in the broader sense clonally propagated mutants with clear-cut phenotypes, such as different color or shifted ripening time, that result in major phenotypic and physiological differences as well as changes in important viticultural traits. Specifically, the cultivars 'Pinot Noir' (PN) and 'Pinot Noir Precoce' (PNP, early ripening) flower at the same time, but vary for the beginning of berry ripening (véraison) and consequently for the harvest time. Apart from the genotype, seasonal climatic conditions (i.e. high temperatures) also affect ripening times. To reveal possible ripening-regulatory genes affecting the timing of the start of ripening, we investigated differences in gene expression profiles between PN and PNP throughout berry development with a closely meshed time series and in two years. Results The difference in the duration of berry formation between PN and PNP was quantified to be about two weeks under the growth conditions applied, using plant material with a proven clonal relationship of PN and PNP. Clusters of co-expressed genes and differentially expressed genes (DEGs) were detected which reflect the shift in the beginning of ripening at the level of gene expression profiles. Functional annotation of these DEGs fits to phenotypic and physiological changes during berry development. In total, we observed between PN and PNP 3,342 DEGs in 2014 and 2,745 DEGs in 2017. The intersection of both years comprises 1,923 DEGs. Among these, 388 DEGs were identified as véraison-specific and 12 were considered as candidates for a regulatory effect on berry ripening time. The expression profiles revealed two candidate genes for Ripening Time Control, designated VviRTIC1 and VviRTIC2 (VIT_210s0071g01145 and VIT_200s0366g00020, respectively) that may contribute to controlling the phenotypic difference between PN and PNP. Conclusions Many of the 1,923 DEGs identified show highly similar expression profiles in both cultivars as far as accelerated berry formation of PNP is concerned. Putative ripening-regulatory genes differentially expressed between PNP and PN as well as véraison-specific genes were identified. We point out potential connections of these genes to molecular events during berry development and discuss potential ripening time controlling candidate genes, two of which are already differentially expressed in the early berry development phase. Several down-regulated genes are annotated to encode auxin response factors / ARFs. Conceivably, changes in auxin signaling may realize the earlier ripening phenotype of PNP.

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Transcriptomic analysis of temporal shifts in berry development between two grapevine cultivars of the Pinot family reveals potential genes controlling ripening time

BMC Plant Biology ◽

10.1186/s12870-021-03110-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Jens Theine ◽

Daniela Holtgräwe ◽

Katja Herzog ◽

Florian Schwander ◽

Anna Kicherer ◽

...

Keyword(s):

Candidate Genes ◽

Expression Profiles ◽

Climatic Conditions ◽

Pinot Noir ◽

Differentially Expressed ◽

Auxin Signaling ◽

Potential Candidate ◽

Berry Development ◽

Ripening Time ◽

Berry Ripening

Abstract Background Grapevine cultivars of the Pinot family represent clonally propagated mutants with major phenotypic and physiological differences, such as different colour or shifted ripening time, as well as changes in important viticultural traits. Specifically, the cultivars ‘Pinot Noir’ (PN) and ‘Pinot Noir Precoce’ (PNP, early ripening) flower at the same time, but vary in the beginning of berry ripening (veraison) and, consequently, harvest time. In addition to genotype, seasonal climatic conditions (i.e. high temperatures) also affect ripening times. To reveal possible regulatory genes that affect the timing of veraison onset, we investigated differences in gene expression profiles between PN and PNP throughout berry development with a closely meshed time series and over two separate years. Results The difference in the duration of berry formation between PN and PNP was quantified to be approximately two weeks under the growth conditions applied, using plant material with a proven PN and PNP clonal relationship. Clusters of co-expressed genes and differentially expressed genes (DEGs) were detected which reflect the shift in the timing of veraison onset. Functional annotation of these DEGs fit to observed phenotypic and physiological changes during berry development. In total, we observed 3,342 DEGs in 2014 and 2,745 DEGs in 2017 between PN and PNP, with 1,923 DEGs across both years. Among these, 388 DEGs were identified as veraison-specific and 12 were considered as berry ripening time regulatory candidates. The expression profiles revealed two candidate genes for ripening time control which we designated VviRTIC1 and VviRTIC2 (VIT_210s0071g01145 and VIT_200s0366g00020, respectively). These genes likely contribute the phenotypic differences observed between PN and PNP. Conclusions Many of the 1,923 DEGs show highly similar expression profiles in both cultivars if the patterns are aligned according to developmental stage. In our work, putative genes differentially expressed between PNP and PN which could control ripening time as well as veraison-specific genes were identified. We point out connections of these genes to molecular events during berry development and discuss potential candidate genes which may control ripening time. Two of these candidates were observed to be differentially expressed in the early berry development phase. Several down-regulated genes during berry ripening are annotated as auxin response factors / ARFs. Conceivably, general changes in auxin signaling may cause the earlier ripening phenotype of PNP.

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Transcriptome Analysis Reveals Differentially Expressed Genes and Long Non-coding RNAs Associated With Fecundity in Sheep Hypothalamus With Different FecB Genotypes

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.633747 ◽

2021 ◽

Vol 9 ◽

Author(s):

Si Chen ◽

Xiaofei Guo ◽

Xiaoyun He ◽

Ran Di ◽

Xiaosheng Zhang ◽

...

Keyword(s):

Functional Annotation ◽

Target Genes ◽

Expression Profiles ◽

Regulatory Elements ◽

Reproductive Hormones ◽

Differentially Expressed ◽

Wild Type ◽

Reproductive Process ◽

Gnrh Secretion ◽

Non Coding Rnas

Small-tailed Han sheep, with different FecB genotypes, manifest distinct ovulation rates and fecundities, which are due to differences in reproductive hormones secreted by the hypothalamic–pituitary–ovarian axis. Nevertheless, the function of the hypothalamus against a FecB mutant background on increasing ovulation rate is rarely reported. Therefore, we determined the expression profiles of hypothalamus tissue collected from six wild-type (WW) and six FecB mutant homozygous (BB) ewes at the follicular and luteal phases by whole-transcriptome sequencing. We identified 53 differentially expressed mRNAs (DEGs) and 40 differentially expressed long non-coding RNAs (DELs) between the two estrus states. Functional annotation analysis revealed that one of the DEGs, PRL, was particularly enriched in the hypothalamic function, hormone-related, and reproductive pathways. The lncRNA–target gene interaction networks and KEGG analysis in combination suggest that the lncRNAs LINC-676 and WNT3-AS cis-acting on DRD2 and WNT9B in different phases may induce gonadotropin-releasing hormone (GnRH) secretion. Furthermore, there were differences of regulatory elements and WNT gene family members involved in the follicular–luteal transition in the reproductive process between wild-type (WNT7A) and FecB mutant sheep (WNT9B). We combined the DEG and DEL data sets screened from different estrus states and genotypes. The overlap of these two sets was identified to select the mRNAs and lncRNAs that have major effects on ovulation. Among the overlapping molecules, seven DEGs and four DELs were involved in the follicular–luteal transition regulated by FecB mutation. Functional annotation analysis showed that two DEGs (FKBP5 and KITLG) were enriched in melanogenesis, oxytocin, and GnRH secretion. LINC-219386 and IGF2-AS were highly expressed in the BB ewes compared with WW ewes, modulating their target genes (DMXL2 and IGF2) to produce more GnRH during follicular development, which explains why mutated ewes produced more mature follicles. These results from expression profiling of the hypothalamus with the FecB mutation at different estrus states provide new insights into how the hypothalamus regulates ovulation under the effect of the FecB mutation.

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Microarray analysis for identification of Plasmodium-refractoriness candidate genes in mosquitoes

Genome ◽

10.1139/g04-056 ◽

2004 ◽

Vol 47 (6) ◽

pp. 1061-1070 ◽

Cited By ~ 10

Author(s):

Haifeng Chen ◽

Jianxin Wang ◽

Ping Liang ◽

Monica Karsay-Klein ◽

Anthony A James ◽

...

Keyword(s):

Real Time ◽

Malaria Parasite ◽

Expressed Sequence Tag ◽

Expression Profiles ◽

Differentially Expressed ◽

Great Promise ◽

Cdna Clones ◽

Significant Similarity ◽

Susceptible Population ◽

Mosquito Midgut

The identification and cloning of genes conferring mosquito refractoriness to the malaria parasite is critical for understanding malaria transmission mechanisms and holds great promise for developing novel approaches to malaria control. The mosquito midgut is the first major site of interaction between the parasite and the mosquito. Failure of the parasite to negotiate this environment can be a barrier for development and is likely the main cause of mosquito refractoriness. This paper reports a study on Aedes aegypti midgut expressed sequence tag (EST) identification and the determination of genes differentially expressed in mosquito populations susceptible and refractory to the avian malaria parasite Plasmodium gallinaceum. We sequenced a total of 1200 cDNA clones and obtained 1183 high-quality mosquito midgut ESTs that were computationally collapsed into 105 contigs and 251 singlets. All 1200 midgut cDNA clones, together with an additional 102 genetically or physically mapped Ae. aegypti clones, were spotted on single arrays with 12 replicates. Of those interrogated microarray elements, 28 (2.3%) were differentially expressed between the susceptible and refractory mosquito populations. Twenty-seven elements showed at least a two-fold increase in expression in the susceptible population level relative to the refractory population and one clone showed reduced expression. Sequence analysis of these differentially expressed genes revealed that 10 showed no significant similarity to any known genes, 6 clones had matches with unannotated genes of Anopheles gambiae, and 12 clones exhibited significant similarity to known genes. Real-time quantitative RT-PCR of selected clones confirmed the mRNA expression profiles from the microarray analysis.Key words: microarray, vector competence, real-time PCR, EST.

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Comparative Transcriptome Analysis Reveals Candidate Genes Involved in Isoquinoline Alkaloid Biosynthesis in Stephania tetrandra

Planta Medica ◽

10.1055/a-1209-3407 ◽

2020 ◽

Vol 86 (17) ◽

pp. 1258-1268

Author(s):

Yangyang Zhang ◽

Yun Kang ◽

Hui Xie ◽

Yaqin Wang ◽

Yaoting Li ◽

...

Keyword(s):

Candidate Genes ◽

Differentially Expressed Genes ◽

Transcriptome Analysis ◽

Expression Profiles ◽

Isoquinoline Alkaloid ◽

Differentially Expressed ◽

Comparative Transcriptome ◽

Isoquinoline Alkaloids ◽

Alkaloid Biosynthesis ◽

Isoquinoline Alkaloid Biosynthesis

AbstractThe roots of Stephania tetrandra are used as a traditional Chinese medicine. Isoquinoline alkaloids are considered to be the most important and effective components in this herb, but little is known about the molecular mechanism underlying their biosynthesis. In this context, this study aimed to reveal candidate genes related to isoquinoline alkaloid biosynthesis in S. tetrandra. Determination of tetrandrine and fangchinoline in the roots and leaves of S. tetrandra by HPLC showed that the roots had much higher contents of the two isoquinoline alkaloids than the leaves. Thus, a comparative transcriptome analysis of the two tissues was performed to uncover candidate genes involved in isoquinoline alkaloid biosynthesis. A total of 71 674 unigenes was obtained and 31 994 of these were assigned putative functions based on BLAST searches against 6 annotation databases. Among the 79 isoquinoline alkaloid-related unigenes, 51 were differentially expressed, with 42 and 9 genes upregulated and downregulated, respectively, when the roots were compared with the leaves. The upregulated differentially expressed genes were consistent with isoquinoline alkaloid accumulation in roots and thus were deemed key candidate genes for isoquinoline alkaloid biosynthesis in the roots. Moreover, the expression profiles of 10 isoquinoline alkaloid-related differentially expressed genes between roots and leaves were validated by quantitative real-time polymerase chain reaction, which indicated that our transcriptome and gene expression profiles were reliable. This study not only provides a valuable genomic resource for S. tetrandra but also proposes candidate genes involved in isoquinoline alkaloid biosynthesis and transcription factors related to the regulation of isoquinoline alkaloid biosynthesis. The results lay a foundation for further studies on isoquinoline alkaloid biosynthesis in this medicinal plant.

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Molecular analysis of anthocyanin biosynthesis-related genes reveal BoTT8 associated with purple hypocotyl of broccoli (Brassica oleracea var. italica L.)

Genome ◽

10.1139/gen-2018-0173 ◽

2019 ◽

Vol 62 (4) ◽

pp. 253-266 ◽

Cited By ~ 2

Author(s):

Md Abdur Rahim ◽

Khandker Shazia Afrin ◽

Hee-Jeong Jung ◽

Hoy-Taek Kim ◽

Jong-In Park ◽

...

Keyword(s):

Molecular Markers ◽

Environmental Factors ◽

Brassica Oleracea ◽

Candidate Genes ◽

Anthocyanin Biosynthesis ◽

Expression Profiles ◽

Market Value ◽

Breeding Programs ◽

Qrt Pcr ◽

Early Seedling

Broccoli (Brassica oleracea var. italica L.) is a highly nutritious vegetable that typically forms pure green or purple florets. However, green broccoli florets sometimes accumulate slight purplish pigmentation in response environmental factors, decreasing their market value. In the present study, we aimed to develop molecular markers to distinguish broccoli genotypes as pure green or purplish floret color at the early seedling stage. Anthocyanins are known to be involved in the purple pigmentation in plants. The purplish broccoli lines were shown to accumulate purple pigmentation in the hypocotyls of very young seedlings; therefore, the expression profiles of the structural and regulatory genes of anthocyanin biosynthesis were analyzed in the hypocotyls using qRT-PCR. BoPAL, BoDFR, BoMYB114, BoTT8, BoMYC1.1, BoMYC1.2, and BoTTG1 were identified as putative candidate genes responsible for the purple hypocotyl color. BoTT8 was much more highly expressed in the purple than green hypocotyls; therefore, it was cloned and sequenced from various broccoli lines, revealing SNP and InDel variations between these genotypes. We tested four SNPs (G > A; A > T; G > C; T > G) in the first three exons and a 14-bp InDel (ATATTTATATATAT) in the BoTT8 promoter in 51 broccoli genotypes, and we found these genetic variations could distinguish the green lines, purple lines, and F1 hybrids. These novel molecular markers could be useful in broccoli breeding programs to develop a true green or purple broccoli cultivar.

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Beryllium-induced lung disease exhibits expression profiles similar to sarcoidosis

European Respiratory Journal ◽

10.1183/13993003.01469-2015 ◽

2016 ◽

Vol 47 (6) ◽

pp. 1797-1808 ◽

Cited By ~ 12

Author(s):

Li Li ◽

Lori J. Silveira ◽

Nabeel Hamzeh ◽

May Gillespie ◽

Peggy M. Mroz ◽

...

Keyword(s):

Gene Expression ◽

Candidate Genes ◽

Differentially Expressed Genes ◽

Mononuclear Cells ◽

Expression Profiles ◽

Differentially Expressed Gene ◽

Janus Kinase ◽

Differentially Expressed ◽

Peripheral Blood Mononuclear ◽

Depth Analysis

A subset of beryllium-exposed workers develop beryllium sensitisation (BeS) which precedes chronic beryllium disease (CBD). We conducted an in-depth analysis of differentially expressed candidate genes in CBD.We performed Affymetrix GeneChip 1.0 ST array analysis on peripheral blood mononuclear cells (PBMCs) from 10 CBD, 10 BeS and 10 beryllium-exposed, nondiseased controls stimulated with BeSO4or medium. The differentially expressed genes were validated by high-throughput real-time PCR in this group and in an additional group of cases and nonexposed controls. The functional roles of the top candidate genes in CBD were assessed using a pharmacological inhibitor. CBD gene expression data were compared with whole blood and lung tissue in sarcoidosis from the Gene Expression Omnibus.We confirmed almost 450 genes that were significantly differentially expressed between CBD and controls. The top enrichment of genes was for JAK (Janus kinase)–STAT (signal transducer and activator of transcription) signalling. A JAK2 inhibitor significantly decreased tumour necrosis factor-α and interferon-γ production. Furthermore, we found 287 differentially expressed genes overlapped in CBD/sarcoidosis. The top shared pathways included cytokine–cytokine receptor interactions, and Toll-like receptor, chemokine and JAK–STAT signalling pathways.We show that PBMCs demonstrate differentially expressed gene profiles relevant to the immunnopathogenesis of CBD. CBD and sarcoidosis share similar differential expression of pathogenic genes and pathways.

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