Homo sapiens
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PROVIDER: PRJNA305437 | ENA |
REPOSITORIES: ENA
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Project description:Transcriptomic alterations in Trypanosoma cruzi-infected cardiac myocytes
| PRJNA119013 | ENA
Project description:Trypanosoma cruzi infection is a major cause of cardiomyopathy. Gene profiling studies of hearts from infected mice have revealed prominent changes in gene expression within many functional pathways. This variety of transcriptomic changes in infected mice raises the question of whether gene expression alterations in whole hearts are due to changes in infected cardiac myocytes or other cells or even to systemic effects of the infection on the heart. We employed microarrays to examine infected cardiac myocyte cultures 48 hr post-infection. Statistical comparison of gene expression levels of 2,258 well annotated unigenes in four independent cultures of infected and uninfected myocytes detected (p < 0.05) significant > 1.5 absolute fold changes in 221 (8.8%) of the sampled genes. Major categories of affected genes included those involved in immune response, extracellular matrix and cell adhesion. While changes in extracellular matrix and cell adhesion genes were anticipated, modulation of immune response genes in the infected myocytes was surprising. These findings on infected cardiac myocytes in culture reveal that altered gene expression described in the heart in Chagas disease are the consequence of both direct infection of the myocytes and resulting from presence of other cell types in the myocardium and systemic effects of infection. Transcriptomic alteration in neonatal mouse cultured cardiomyocytes induced by the parasite T.cruzi were detected by profiling and compared using AECOM mouse 32k oligonucleotide arrays hybridized in the "multiple yellow" strategy described in Iacobas et al, Biochem Biophys Res Commun. 2006 349(1):329-38.
2010-05-15 | E-GEOD-17330 | biostudies-arrayexpress
Project description:Trypanosoma cruzi infection is a major cause of cardiomyopathy. Gene profiling studies of hearts from infected mice have revealed prominent changes in gene expression within many functional pathways. This variety of transcriptomic changes in infected mice raises the question of whether gene expression alterations in whole hearts are due to changes in infected cardiac myocytes or other cells or even to systemic effects of the infection on the heart. We employed microarrays to examine infected cardiac myocyte cultures 48 hr post-infection. Statistical comparison of gene expression levels of 2,258 well annotated unigenes in four independent cultures of infected and uninfected myocytes detected (p < 0.05) significant > 1.5 absolute fold changes in 221 (8.8%) of the sampled genes. Major categories of affected genes included those involved in immune response, extracellular matrix and cell adhesion. While changes in extracellular matrix and cell adhesion genes were anticipated, modulation of immune response genes in the infected myocytes was surprising. These findings on infected cardiac myocytes in culture reveal that altered gene expression described in the heart in Chagas disease are the consequence of both direct infection of the myocytes and resulting from presence of other cell types in the myocardium and systemic effects of infection.
2009-08-04 | GSE17330 | GEO
Project description:The molecular mechanisms of Trypanosoma cruzi induced cardiac fibrosis remains to be elucidated. Primary human cardiomyoctes (PHCM) exposed to invasive T. cruzi trypomastigotes were used for transcriptome profiling and downstream bioinformatic analysis to determine fibrotic-associated genes regulated early during infection process (0 to 120 minutes). The identification of early molecular host responses to T. cruzi infection can be exploited to delineate important molecular signatures that can be used for the classification of Chagasic patients at risk of developing heart disease. Our results show distinct gene network architecture with multiple gene networks modulated by the parasite with an incline towards progression to a fibrogenic phenotype. Early during infection, T. cruzi significantly upregulated transcription factors including activator protein 1 (AP1) transcription factor network components (including FOSB, FOS and JUNB), early growth response proteins 1 and 3 (EGR1, EGR3), and cytokines/chemokines (IL5, IL6, IL13, CCL11), which have all been implicated in the onset of fibrosis. The changes in our selected genes of interest did not all start at the same time point. The transcriptome microarray data, validated by quantitative Real-Time PCR, was also confirmed by immunoblotting and customized Enzyme Linked Immunosorbent Assays (ELISA) array showing significant increases in the protein expression levels of fibrogenic EGR1, SNAI1 and IL 6. Furthermore, phosphorylated SMAD2/3 which induces a fibrogenic phenotype is also upregulated accompanied by an increased nuclear translocation of JunB. Pathway analysis of the validated genes and phospho-proteins regulated by the parasite provides the very early fibrotic interactome operating when T. cruzi comes in contact with PHCM. The interactome architecture shows that the parasite induces both TGF-β dependent and independent fibrotic pathways, providing an early molecular foundation for Chagasic cardiomyopathy. Examining the very early molecular events of T. cruzi cellular infection may provide disease biomarkers which will aid clinicians in patient assessment and identification of patient subpopulation at risk of developing Chagasic cardiomyopathy. Primary Human Cardiomyoctes (low passage) were exposed to T. cruzi at different time points. The control was done in biological triplicates and the time points (60, 90 and 120 minutes) were done in biological duplicates.
2015-12-09 | E-GEOD-75821 | biostudies-arrayexpress
Project description:Comparative genomic analysis of Trypanosoma cruzi G with Trypanosoma cruzi D11.
2022-03-06 | GSE197870 | GEO
Project description:The intracellular pathogen Trypanosoma cruzi secretes an activity that blocks TGF-β-dependent induction of connective tissue growth factor (CTGF/CCN2). Here, we address the mechanistic basis for T. cruzi-mediated interference of CTGF/CCN2 expression by examining host cell signaling pathways and the global inhibitory effect on TGF-β-dependent gene expression. We show that the expression of a discrete subset of TGF-β-inducible genes involved in cell proliferation, wound repair, and immune regulation are blocked by the soluble T. cruzi activity, demonstrating that this parasite-derived activity has broad, but specific effects on fibroblast gene regulation. Primary human fibroblasts were treated with TGF-β, T. cruzi conditioned medium (PCM) and TGF-β/ PCM simultaneously. Untreated cells were also included as controls. Total RNA was extracted and gene expression levels analyzed with Affymetrix microarrays. Three independent biological replicates were included for each type of treatment.
2011-09-08 | E-GEOD-16416 | biostudies-arrayexpress
Project description:Trypanosoma cruzi dysregulates the gene expression profile of primary human cardiomyocytes (PHCM) during the early phase of infection through a mechanism which remains to be elucidated. The role that small non-coding RNAs (sncRNA) including PIWI-interacting RNA (piRNA) play in regulating gene expression during the early phase of infection is unknown. To understand how T. cruzi dysregulate gene expression in the heart, we challenged PHCM with T. cruzi trypomastigotes and analyzed sncRNA, especially piRNA, by RNA-sequencing. The parasite induced significant differential expression of host piRNAs. An average of 21,595,866 (88.40%) of clean reads mapped to the human reference genome. The parasite induced 217 unique piRNAs that were significantly differentially expressed (q ≥ 0.8). Of these differentially expressed piRNAs, 6 were known and 211 were novel piRNAs. In silico analysis showed that some of the dysregulated known and novel piRNAs could target and potentially regulate the expression of genes reported to play important roles during T. cruzi infection. This is the first report showing that T. cruzi can induce differential expression of piRNAs in PHCM, advancing our knowledge about the involvement of piRNAs in an infectious disease model.
2021-12-28 | GSE192658 | GEO
Project description:The molecular mechanisms of Trypanosoma cruzi induced cardiac fibrosis remains to be elucidated. Primary human cardiomyoctes (PHCM) exposed to invasive T. cruzi trypomastigotes were used for transcriptome profiling and downstream bioinformatic analysis to determine fibrotic-associated genes regulated early during infection process (0 to 120 minutes). The identification of early molecular host responses to T. cruzi infection can be exploited to delineate important molecular signatures that can be used for the classification of Chagasic patients at risk of developing heart disease. Our results show distinct gene network architecture with multiple gene networks modulated by the parasite with an incline towards progression to a fibrogenic phenotype. Early during infection, T. cruzi significantly upregulated transcription factors including activator protein 1 (AP1) transcription factor network components (including FOSB, FOS and JUNB), early growth response proteins 1 and 3 (EGR1, EGR3), and cytokines/chemokines (IL5, IL6, IL13, CCL11), which have all been implicated in the onset of fibrosis. The changes in our selected genes of interest did not all start at the same time point. The transcriptome microarray data, validated by quantitative Real-Time PCR, was also confirmed by immunoblotting and customized Enzyme Linked Immunosorbent Assays (ELISA) array showing significant increases in the protein expression levels of fibrogenic EGR1, SNAI1 and IL 6. Furthermore, phosphorylated SMAD2/3 which induces a fibrogenic phenotype is also upregulated accompanied by an increased nuclear translocation of JunB. Pathway analysis of the validated genes and phospho-proteins regulated by the parasite provides the very early fibrotic interactome operating when T. cruzi comes in contact with PHCM. The interactome architecture shows that the parasite induces both TGF-β dependent and independent fibrotic pathways, providing an early molecular foundation for Chagasic cardiomyopathy. Examining the very early molecular events of T. cruzi cellular infection may provide disease biomarkers which will aid clinicians in patient assessment and identification of patient subpopulation at risk of developing Chagasic cardiomyopathy.
2015-12-09 | GSE75821 | GEO
Project description:As Trypanosoma cruzi, the etiological agent of Chagas disease, multiplies in the cytoplasm of nucleated host cells, infection with this parasite is highly likely to affect host cells. We performed an exhaustive transcriptome analysis of T. cruzi-infected HeLa cells using an oligonucleotide microarray containing probes for greater than 47,000 human gene transcripts. In comparison with uninfected cells, those infected with T. cruzi showed greater than threefold up-regulation of 41 genes and greater than threefold down-regulation of 23 genes. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) of selected, differentially expressed genes confirmed the microarray data. Many of these up- and down-regulated genes were related to cellular proliferation, including seven up-regulated genes encoding proliferation inhibitors and three down-regulated genes encoding proliferation promoters, strongly suggesting that T. cruzi infection inhibits host cell proliferation, which may allow more time for T. cruzi to replicate and produce its intracellular nests. These findings provide new insight into the molecular mechanisms by which intracellular T. cruzi infection influences the host cell, leading to pathogenicity. Keywords: infection response
2008-02-06 | GSE7047 | GEO