Molecular Alterations of Extracellular Matrix in the Brain of Newborns with Congenital Zika Syndrome
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA516806 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8481464_1.fastq.gz | Fastqsanger.gz | |||
| SRR8481464_2.fastq.gz | Fastqsanger.gz | |||
| SRR8481465_1.fastq.gz | Fastqsanger.gz | |||
| SRR8481465_2.fastq.gz | Fastqsanger.gz | |||
| SRR8481466_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 8 |
Similar Datasets
Project description:Zika virus (ZIKV) infection during pregnancy could cause a set of severe abnormalities in the fetus known as congenital Zika syndrome (CZS). Experiments using animal models and in vitro systems significantly contributed to our understanding of the physiopathology of ZIKV infection. However, the molecular basis of CZS is not yet studied in humans. Here, we used a systems biology approach to integrate transcriptomic, proteomic and genomic data from post-mortem brains of neonates with CZS. We observed that collagen genes were greatly reduced in CZS brains at both the RNA and protein levels and that neonates with CZS have several polymorphisms in collagen genes associated with osteogenesis imperfect and arthrogryposis. These findings were validated using immunohistochemistry and collagen staining of ZIKV infected and non-infected samples. Additionally, it was found that cell adhesion genes that are essential for neurite outgrowth and axon guidance were up-regulated and thereby confirmed the neuronal migration defects observed. This work provided new insights into the underlying mechanisms of CZS and revealed host genes associated with CZS susceptibility.
2020-05-18 | GSE125554 | GEO
Project description:Congenital Zika syndrome (CZS), caused by Zika virus (ZIKV) infection, has been associated to impairment of early brain development, particularly related to neural progenitor cells (NPCs) survival and growth. In this work we report in a high-throughput manner (RNA-Seq) the differences in the transcriptomes of hiPSCs(human induced pluripotent stem cells)-derived NPCs from 3 pairs of discordant twins for Congenital Zika syndrome (CZS). We found significant differences in the expression levels of genes relevant to the regulation of neural development between the NPCs from CZS-affected and non-affected twins, suggesting that epigenetic differences may contribute to the different susceptibilities of NPCs to ZIKV infection.
2018-02-27 | GSE102128 | GEO
Project description:During pregnancy, the Zika virus (ZIKV) can be vertically transmitted, causing Congenital Zika Syndrome (CZS) in fetuses. ZIKV infection in early gestational trimesters increases the chances to develop CZS. This syndrome involves several pathologies with a difficult diagnosis, which usually occurs in the postnatal stage. In this work, we aim to identify biological processes and molecular pathways related to CZS development and propose a series of putative protein and metabolite biomarkers for CZS prognosis in early pregnancy trimesters. Twenty-five serum samples of pregnant women were analyzed. For biological analysis, samples were separated into 3 biological groups composed of a control group of healthy pregnant women and two groups of ZIKV-infected pregnant women bearing non- microcephalic and microcephalic fetuses. Control and ZIKV-infected groups - without microcephalic fetuses - were subdivided into healthy and Cognitive Developmental Delay (CDD) newborns for biomarker analysis. We detected over 1,000 proteins and 500 metabolites by bottom-up proteomics and untargeted metabolomics, respectively. Statistical approaches - (t-Student, Limma, ANOVA, and DIABLO) - were applied to find CZS differentially abundant proteins (DAP) and metabolites (DAM). Enrichment analysis (i.e., biological processes and molecular pathways) of the DAP and the DAM allowed us to identify the ECM organization and proteoglycans, amino acid metabolism, and arachidonic acid metabolism as signatures in the CZS development. Five proteins and four metabolites were selected as CZS biomarkers candidates. The protein-based model indicated superior performance values for the Vitamin K-dependent protein S, Selenoprotein P, Inter-alpha- trypsin inhibitor heavy chain H2, Kallistatin, and Protein Z-dependent protease inhibitor proteins. Furthermore, the metabolite-based model was able to predict CZS with a probability of 90%. Serum multi-omics analysis led us to propose for further studies nine potential biomarkers for CZS early prognosis with high sensitivity and specificity.
2024-07-02 | PXD043324 | Pride
Project description:GENETIC EVALUATION IN CHILDREN WITH EYE ANOMALIES ASSOCIATED WITH CONGENITAL ZIKA SYNDROME
| PRJEB40869 | ENA
Project description:In this study, we analyzed by a shotgun proteomic approach the amniotic fluid of pregnant women infected with Zika carrying microcephalic (ZIKV+M+) or healthy fetuses (ZIKV+M-) compared to Zika negative controls (ZIKV-M-) to identify and understand the biological process and pathways affected by CZS development. Up-abundant proteins in the ZIKV+M- group showed enrichment mainly in the extracellular matrix (ECM) structure and organization. The innate immune system (i.e. neutrophil degranulation) and fibrin clot formation processes were dysregulated in the ZIKV+M+ group, with an increase in the abundance of proteins associated with these biological processes. In both groups, a decrease in the abundance of proteins associated with neutrophil degranulation was observed. ZIKV+M+ group presented a decrease of abundance in the dysregulated extracellular matrix proteins compared to ZIKV+M-. These results could suggest that the development of microcephalic or healthy phenotypes is more associated with the ECM and immune system protein abundances than the dysregulated processes in each group.
2024-07-02 | PXD023776 | Pride
Project description:Background: Congenital heart disease (CHD) lesions are the most common birth defects and are associated with life-long neurodevelopmental risks. The exact mechanism by which CHD and neurodevelopment are linked remains unclear; exploring the epigenome in these cases may provide novel insights into predictive biomarkers contributing to outcomes. The present study characterizes the impact of CHD on the newborn epigenome and uncovers potential differences in epigenetic age that may underpin long-term neurodevelopmental disabilities in this high-risk population. Methods: This is a prospective, single-site case-control study conducted at Children’s National Hospital with subjects enrolled from the Washington DC Metropolitan area. Genomic samples were collected between 2018 and 2024 and analyzed using the Illumina MethylationEPIC BeadChip array platform. PedBE was used to assess infant biological age acceleration. Results: Using a methylation array approach, analysis of 33 newborns with complex CHD requiring neonatal cardiac surgery and 26 healthy controls. There was a significant accelerated epigenetic age in newborns with CHD compared to newborns from uncomplicated pregnancies (p < 0.001). Further subgroup analysis within the CHD cohort revealed that both single- and two-ventricle CHD displayed significant accelerated epigenetic age, with transposition of the great arteries (TGA) cases specifically having the greatest accelerated age (107.2 days, p = 0.0001). Further analysis of the CHD group revealed significant age acceleration associated with low blood oxygen saturation. Conclusions: The present study reveals novel epigenomic signatures newborns with CHD. The functional significance of these findings, specifically accelerated epigenetic age, should be the focus of future analyses to uncover correlations associated with related outcomes. These studies aim to advance our understanding of mechanisms underlying long-term neurodevelopmental and behavioral impairment in these patients.
2025-07-09 | GSE293799 | GEO
Project description:Comparison of the transcriptome of naive (CD45RA+ CD27+) and differentiated (CD27-CD28-) CD4+ lymphocytes from newborns with congenital human cytomegalovirus infection (cord blood samples) and pregnant women diagnosed with primary CMV infection. Naive cells from HCMV uninfected newborns were used as a control.
2015-01-18 | E-MEXP-3473 | biostudies-arrayexpress
Project description:Zika virus (ZIKV) can be transmitted vertically to the fetus, having a high chance to develop Congenital Zika Syndrome (CZS). Studies have shown that ZIKV impairs brain development. However, little is known about the molecular differences between non- microcephalic ZIKV-infected fetuses and microcephalic ones. Here, our main goal is to identify the alterations in the amniotic fluid (AF) metabolome in ZIKV-infected patients and their relation to CZS progression. We applied an untargeted metabolomics strategy to analyze seven AF of pregnant women: healthy women and ZIKV-infected women bearing non-microcephalic and microcephalic fetuses. Infected patients were characterized by glycerophospholipid metabolism impairment, which is accentuated in microcephalic phenotypes. Glycerophospholipid decreased concentration in AF can be a consequence of intracellular transport of lipids to the placental or fetal tissues under development. The increased intracellular concentration of lipids can lead to mitochondrial dysfunction and neurodegeneration caused by lipid droplet accumulation. Furthermore, the dysregulation of amino acid metabolism was a molecular fingerprint of microcephalic phenotypes, specifically serine, and proline metabolisms. Both amino acid deficiencies were related to neurodegenerative disorders, intrauterine growth retardation, and placental abnormalities. This study contributes to the understanding of CZS pathology and discovering potential biomarkers for CZS prognosis in the early stages of pregnancy.
2025-09-04 | PXD039643 | Pride
Project description:Collagen VI (COLVI) is a non-fibrillar collagen expressed in skeletal muscle and most connective tissues. Mutations in COLVI genes cause two major clinical forms, Bethlem myopathy and Ullrich congenital muscular dystrophy (UCMD). In addition to congenital muscle weakness, patients affected by COLVI myopathies show axial and proximal joint contractures and distal joint hypermobility, which suggest the involvement of the tendon function. We examined a peroneal tendon biopsy and tenocyte culture of a 15-year-old patient affected by UCMD with compound heterozygous COL6A2 mutations. In patient's tendon biopsy, we found striking morphological alterations of tendon fibrils, consisting in irregular profiles and reduced mean diameter. The organization of the pericellular matrix of tenocytes, the primary site of collagen fibril assembly, was severely affected, as determined by immunoelectron microscopy, which showed an abnormal accumulation of COLVI and altered distribution of collagen I (COLI) and fibronectin (FBN). In patient's tenocyte culture, COLVI web formation and cell surface association were severely impaired; large aggregates of COLVI, which matched with COLI labeling, were frequently detected in the extracellular matrix. In addition, metalloproteinase MMP-2, an extracellular matrix-regulating enzyme, was increased in the conditioned medium of patient's tenocytes, as determined by gelatin zymography and western blot. Altogether, these data indicate that COLVI deficiency may influence the organization of UCMD tendon matrix, resulting in dysfunctional fibrillogenesis. The alterations of tendon matrix may contribute to the complex pathogenesis of COLVI related myopathies.
| S-EPMC4896961 | biostudies-literature
Project description:Genome-wide DNA methylation profiling of over 850,000 methylation sites carried out using the Illumina MethylationEPIC BeadChip was used to compare 18 babies born with congenital Zika virus microcephaly, 7 babies exposed to Zika virus in utero but born without clinical signs, and 20 control unexposed unaffected babies
2020-07-20 | GSE145233 | GEO