Integrating lncRNAs and mRNAs expression profiles in penicillin-induced persistent chlamydial infection in HeLa cells
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PROVIDER: PRJNA748386 | ENA |
REPOSITORIES: ENA
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Project description:Chlamydia trachomatis (C. trachomatis) is a major etiological agent of sexually transmitted infection. Some stressing conditions can result in persistent chlamydial infection, which is thought to associate with severe complications such as ectopic pregnancy and tubal factor infertility. Long noncoding RNAs (lncRNAs) have been identified as key modulators in many biological processes. However, the role of lncRNAs in persistent chlamydial infection is still unclear. In this study, we used lncRNA and mRNA microarray to identify the global lncRNAs and mRNAs expression in penicillin-induced persistent chlamydial infection in HeLa cells as well as the control group (HeLa cells without C. trachomatis infection). Among 1005 differentially expressed lncRNAs, 585 lncRNAs were upregulated and 420 downregulated in persistent chlamydial infection, while 410 mRNAs were identified to express differentially, of which 113 mRNAs were upregulated and 297 downregulated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis with differentially expressed genes were performed. We then constructed the lncRNA-miRNA-mRNA competing endogenous RNAs (ceRNAs) network. Four mRNAs were validated to be changed by quantitative real-time PCR which were correlated with the microarray result. Integration of protein-protein interaction (PPI) network was constructed and hub genes were identified. These findings provide a new perspective on the molecular mechanism of penicillin-induced persistent chlamydial infection.
2022-02-14 | GSE180478 | GEO
Project description:NK cells and pulmonary macrophages both are important components of innate immunity. The interaction between NK cells and pulmonary macrophages during Chlamydia muridarum（C. muridarum）respiratory infections is poorly understood. In this study, we explored the effect of NK cells on regulation of pulmonary macrophage function during chlamydial lung infection. We found that NK depletion led to polarization of pulmonary macrophages from M1 to M2 phenotype, and this related to significantly reduced miR-155 expression in pulmonary macrophage. Using adoptive transfer approach, we found that the recipient mice receiving lung macrophages isolated from C. muridarum-infected NK-cell-depleted mice exhibited an increased bacterial load and severe inflammation in the lung upon chlamydial challenge when compared with the recipients of lung macrophages from infected IgG -treated mice. Herein, the effects of NK cells on macrophage polarization were examined in vitro. We found that NK cells from chlamydial-infected mice (iNK) significantly induced M1 polarization compared to that from sham-infected mice (uNK). Inhibition of miR-155 expression in macrophages attenuated M1 polarization induced by iNK, while miR-155 over-expression enhanced it. Furthermore, neutralization of IFN-γ in the coculture system decreased the expression of miR-155 by macrophages, and resulted in diminished M1 polarization induced by iNK cells. The data indicates that NK cells direct M1 polarization through up-regulation of miR-155 by IFN-γ production, and NK-regulated macrophage polarization is functionally relevant to host defense against chlamydial infection.
2022-01-26 | GSE183577 | GEO
Project description:Chlamydiae are obligate intracellular bacteria comprising well-known human pathogens and ubiquitous symbionts of protists, which are characterized by a unique developmental cycle. Here we comprehensively analyzed gene expression dynamics of Protochlamydia amoebophila during infection of its Acanthamoeba host by RNA sequencing. This revealed a highly dynamic transcriptional landscape, where major transcriptional shifts are conserved among chlamydial symbionts and pathogens. Our data served to propose a time-resolved model for type III protein secretion during the developmental cycle, and we provide evidence for a biphasic metabolism of P. amoebophila during infection, which involves energy parasitism and amino acids as carbon source during initial stages and a post-replicative switch to endogenous glucose-based ATP production. This fits well with major transcriptional changes in the amoeba host, where upregulation of complex sugar breakdown precedes the P. amoebophila metabolic switch. The biphasic chlamydial metabolism represents a unique adaptation to exploit eukaryotic host cells, which likely contributed to the evolutionary success of this group of microbes.
2017-04-26 | GSE93891 | GEO
Project description:Genital C. trachomatis (CT) infection may cause pelvic inflammatory disease (PID) that can lead to tubal factor infertility (TFI). Understanding the pathogenesis of chlamydial complications including the pathophysiological processes within the female host genital tract is of immense importance in preventing adverse pathology. In this study, we tested the hypothesis that the miRNA profile of a acute primary chlamydial infection characterized by temporary inflammation versus the profile associated with chronic genital chlamydial infections that might precipitate PID or TFI will be different. Thus, we analyzed and compared the differentially expressed miRNAs that regulate CT pathogenesis after a single genital infection and those involved in the development of PID and TFI after repeat infections. Mice (Mus musculus) were infected with Chlamydia muridarum once or twice with a month interval between infections, and then sacrificed and genital tract tissues were collected at 1, 2, 4, and 8 weeks after infection. miRNAs were differentially expressed in both first infection and the re-infection; however, the miRNA expression profile was different for both groups. Pathway analysis showed that, amongst other functions, the differentially regulated miRNA might be regulating several pathways involved in cellular and tissue development, disease conditions and toxicity. Grant number: 1SC2HD086066-03 Funding source: Eunice Kennedy Shriver National Institute of Child Health & Human Development Title: Discovering Novel Biomarkers Predictive of Tubal Infertility Caused by Chlamydia. Principal investigator: Yusuf Omosun Date: 05/01/2015-04/30/2019
2019-01-27 | GSE118396 | GEO
Project description:The mechanism underlying the cervical carcinogenesis mediated by persistent HPV infection remains elusive. Here we pioneeringly deciphered both temporal transition and spatial distribution of the cellular subsets during the disease progression from normal cervix, precancer lesions to cervical cancer by integrating scRNA-seq with ST. We not only identified three ‘HPV-related epithelial clusters’ unique to normal, HSIL and cervical cancer respectively, but also discovered node genes which potentially determined the disease progression. Moreover, we observed a gradual transition of multiple immune cells from positive immune response to dysregulation and exhaustion, to an immune-suppressive microenvironment during the malignant program. Besides, the cellular interaction analysis further verified a ‘homeostasis-balance-malignancy’ change within cervix microenvironment during disease escalation. Together, these findings not only deciphered mysterious persistent HPV infection spatiotemporally from the process of precancer to cervical cancer but also provided unprecedented possibilities for accurate diagnosis, precise treatment and prognosis evaluation for precancer and cervical cancer.
2023-04-02 | GSE208653 | GEO
Project description:The mechanism underlying the cervical carcinogenesis mediated by persistent HPV infection remains elusive. Here we pioneeringly deciphered both temporal transition and spatial distribution of the cellular subsets during the disease progression from normal cervix, precancer lesions to cervical cancer by integrating scRNA-seq with ST. We not only identified three ‘HPV-related epithelial clusters’ unique to normal, HSIL and cervical cancer respectively, but also discovered node genes which potentially determined the disease progression. Moreover, we observed a gradual transition of multiple immune cells from positive immune response to dysregulation and exhaustion, to an immune-suppressive microenvironment during the malignant program. Besides, the cellular interaction analysis further verified a ‘homeostasis-balance-malignancy’ change within cervix microenvironment during disease escalation. Together, these findings not only deciphered mysterious persistent HPV infection spatiotemporally from the process of precancer to cervical cancer but also provided unprecedented possibilities for accurate diagnosis, precise treatment and prognosis evaluation for precancer and cervical cancer.
2023-04-02 | GSE208654 | GEO
Project description:Human-induced pluripotent stem cells (iPSCs) are derived from differentiated somatic cells using defined factors and provide a renewable source of autologous cells for cell therapy. Many reprogramming methods have been employed to generate human iPSCs, including the use of integrating vectors and non-integrating vectors. Maintenance of the genomic integrity of iPSCs is highly desirable if the cells are to be used in clinical applications. Here, using the Affymetrix Cytoscan HD array, we investigated the genomic aberration profiles of 19 human cell lines: 5 embryonic stem cell (ESC) lines, 6 iPSC lines derived using integrating vectors (“integrating iPSC lines”), 6 iPSC lines derived using non-integrating vectors (“non-integrating iPSC lines”), and the 2 parental cell lines from which the iPSCs were derived. The genome-wide copy number variation (CNV), loss of heterozygosity (LOH) and mosaicism patterns of integrating and non-integrating iPSC lines were investigated. The maximum sizes of CNVs in the genomes of the integrating iPSC lines were 20 times higher than those of the non-integrating iPSC lines. Moreover, the total number of CNVs was much higher in integrating iPSC lines than in other cell lines. The average numbers of novel CNVs with a low degree of overlap with the DGV and of likely pathogenic CNVs with a high degree of overlap with the ISCA database were highest in integrating iPSC lines. Different SNP calls revealed that, using the parental cell genotype as a reference, integrating iPSC lines displayed more single nucleotide variations and mosaicism than did non-integrating iPSC lines. This study describes the genome stability of human iPSCs generated using either a DNA-integrating or non-integrating reprogramming method, of the corresponding somatic cells, and of hESCs. Our results highlight the importance of using a high-resolution method to monitor genomic aberrations in iPSCs intended for clinical applications to avoid any negative effects of reprogramming or cell culture. 19 human cell lines: 5 embryonic stem cell (ESC) lines, 6 iPSC lines derived using integrating vectors (“integrating iPSC lines”), 6 iPSC lines derived using non-integrating vectors (“non-integrating iPSC lines”), and the 2 parental cell lines from which the iPSCs were derived.
2015-06-08 | E-GEOD-69632 | biostudies-arrayexpress
Project description:Messenger RNA (mRNA) and long noncoding RNA (lncRNA) are two main subgroups of RNAs participating in transcription regulation. With the development of next generation sequencing, increasing lncRNAs are identified. Many hidden functions of lncRNAs are also revealed. However, the differences in lncRNAs and mRNAs are still unclear. For example, we need to determine whether lncRNAs have stronger tissue specificity than mRNAs and which tissues have more lncRNAs expressed. To investigate such tissue expression difference between mRNAs and lncRNAs, we encoded 9339 lncRNAs and 14,294 mRNAs with 71 expression features, including 69 maximum expression features for 69 types of cells, one feature for the maximum expression in all cells, and one expression specificity feature that was measured as Chao-Shen-corrected Shannon's entropy. With advanced feature selection methods, such as maximum relevance minimum redundancy, incremental feature selection methods, and random forest algorithm, 13 features presented the dissimilarity of lncRNAs and mRNAs. The 11 cell subtype features indicated which cell types of the lncRNAs and mRNAs had the largest expression difference. Such cell subtypes may be the potential cell models for lncRNA identification and function investigation. The expression specificity feature suggested that the cell types to express mRNAs and lncRNAs were different. The maximum expression feature suggested that the maximum expression levels of mRNAs and lncRNAs were different. In addition, the rule learning algorithm, repeated incremental pruning to produce error reduction algorithm, was also employed to produce effective classification rules for classifying lncRNAs and mRNAs, which gave competitive results compared with random forest and could give a clearer picture of different expression patterns between lncRNAs and mRNAs. Results not only revealed the heterogeneous expression pattern of lncRNA and mRNA, but also gave rise to the development of a new tool to identify the potential biological functions of such RNA subgroups.
| S-EPMC6274976 | biostudies-literature
Project description:Biphasic metabolism and host interaction of a chlamydial symbiont
| PRJNA362727 | ENA
Project description:Human-induced pluripotent stem cells (iPSCs) are derived from differentiated somatic cells using defined factors and provide a renewable source of autologous cells for cell therapy. Many reprogramming methods have been employed to generate human iPSCs, including the use of integrating vectors and non-integrating vectors. Maintenance of the genomic integrity of iPSCs is highly desirable if the cells are to be used in clinical applications. Here, using the Affymetrix Cytoscan HD array, we investigated the genomic aberration profiles of 19 human cell lines: 5 embryonic stem cell (ESC) lines, 6 iPSC lines derived using integrating vectors (“integrating iPSC lines”), 6 iPSC lines derived using non-integrating vectors (“non-integrating iPSC lines”), and the 2 parental cell lines from which the iPSCs were derived. The genome-wide copy number variation (CNV), loss of heterozygosity (LOH) and mosaicism patterns of integrating and non-integrating iPSC lines were investigated. The maximum sizes of CNVs in the genomes of the integrating iPSC lines were 20 times higher than those of the non-integrating iPSC lines. Moreover, the total number of CNVs was much higher in integrating iPSC lines than in other cell lines. The average numbers of novel CNVs with a low degree of overlap with the DGV and of likely pathogenic CNVs with a high degree of overlap with the ISCA database were highest in integrating iPSC lines. Different SNP calls revealed that, using the parental cell genotype as a reference, integrating iPSC lines displayed more single nucleotide variations and mosaicism than did non-integrating iPSC lines. This study describes the genome stability of human iPSCs generated using either a DNA-integrating or non-integrating reprogramming method, of the corresponding somatic cells, and of hESCs. Our results highlight the importance of using a high-resolution method to monitor genomic aberrations in iPSCs intended for clinical applications to avoid any negative effects of reprogramming or cell culture.
2015-06-08 | GSE69632 | GEO