Transcriptomic Analysis of Hofbauer Cells from Human Placental Tissue Infected with HIV, CMV, and ZIKV
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ABSTRACT:
PROVIDER: PRJNA1146376 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR30188139_1.fastq.gz | Fastqsanger.gz | |||
| SRR30188139_2.fastq.gz | Fastqsanger.gz | |||
| SRR30188140_1.fastq.gz | Fastqsanger.gz | |||
| SRR30188140_2.fastq.gz | Fastqsanger.gz | |||
| SRR30188141_1.fastq.gz | Fastqsanger.gz |
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Project description:This study involves the isolation of Hofbauer cells from human placental tissue at different gestation periods and their infection with HIV, CMV, and ZIKV. The transcriptomic profiles of these infected cells were analyzed using RNA-sequencing to identify differentially expressed genes and pathways.
2024-09-20 | GSE274414 | GEO
Project description:Here we studied the transcriptional profile of virus specific CD8 T cells to gain molecular insights in CD8 T cell functionality in HIV infection. HIV- and CMV-specific CD8 T cells were isolated from HIV infected individuals participating in the Amsterdam Cohort Studies (HIV progressors, long-term non-progressors (LTNP; HLA-B*57 and non-HLA-B*57) and individuals carrying the MAVS minor genotype) and CMV seropositive blood donors (BD). The transcription profile of HIV-specific CD8 T cells of LTNP groups was associated with increased protein/RNA metabolism pathways, indicating that immune control of HIV infection in these individuals is associated with increased functionality. In contrast, CMV-specific CD8 T cells from progressors showed increased expression of genes related to effector functions and suggests recent CMV reactivation. Our study provides novel insights into molecular mechanisms involved in HIV and CMV control in chronic HIV infection.
2024-10-09 | GSE197333 | GEO
Project description:Bacterial and viral infections of the placenta are associated with inflammation and adverse pregnancy outcomes. Hofbauer cells (HBCs) are specialised fetal-origin macrophages in the placental villi and are proposed to protect the fetus from vertical transmission of pathogens; however, they are poorly understood. Here, we have performed quantitative proteomics on term HBCs under resting conditions and following exposure to bacterial and viral pathogen associated molecular patterns (PAMPs), and investigated the contribution of fetal sex to these responses. Resting HBCs expressed a plethora of proteins pertinent to macrophage function, including chemokines, cytokines, Toll-like receptors, and classical and non-classical major histocompatibility complex class I and II molecules. HBCs mounted divergent responses to bacterial versus viral PAMPs but exhibited protein expression changes suggestive of a switch towards a more pro-inflammatory phenotype. A comparison between male and female HBCs, showed that the latter mounted a much stronger and wider response. Sexual dimorphism in HBCs was primarily associated with lipid metabolism in males and cytoskeleton organisation in females. We provide a novel and comprehensive understanding regarding the phenotype of term placental macrophages and their sex-dependent responses to infectious triggers.
2022-10-31 | PXD033006 | Pride
Project description:Maternal immune activation is associated with adverse offspring neurodevelopmental outcomes, many mediated by in utero microglial programming. As microglia remain inaccessible throughout development, identification of noninvasive biomarkers reflecting fetal brain microglial programming could permit screening and intervention. We used lineage tracing to demonstrate the shared ontogeny between fetal brain macrophages (microglia) and fetal placental macrophages (Hofbauer cells) in a mouse model of maternal diet-induced obesity, and single-cell RNA-seq to demonstrate shared transcriptional programs. Comparison with human datasets demonstrated conservation of placental resident macrophage signatures between mice and humans. Single-cell RNA-seq identified common alterations in fetal microglial and Hofbauer cell gene expression induced by maternal obesity, as well as sex differences in these alterations. We propose that Hofbauer cells, which are easily accessible at birth, provide novel insights into fetal brain microglial programs, and may facilitate the early identification of offspring vulnerable to neurodevelopmental disorders in the setting of maternal exposures.
2024-06-05 | GSE252343 | GEO
Project description:Background: DNA methylation (DNAm) profiling has emerged as a powerful tool for characterizing the placental methylome. However, previous studies have focused primarily on whole placental tissue, which is a mixture of epigenetically distinct cell populations. Here, we present the first methylome-wide analysis of first trimester (n=9) and term (n=19) human placental samples of four cell populations: trophoblasts, Hofbauer cells, endothelial cells, and stromal cells, using the Illumina EPIC methylation array, which quantifies DNAm at >850,000 CpGs. Results: The most distinct DNAm profiles were those of placental trophoblasts, which are central to many pregnancy-essential functions, and Hofbauer cells, which are a rare fetal-derived macrophage population. Cell-specific DNAm occurs at functionally-relevant genes, including genes associated with placental development and preeclampsia. Known placental-specific methylation marks, such as those associated with genomic imprinting, repetitive element hypomethylation, and placental partially methylated domains, were found to be more pronounced in trophoblasts and often absent in Hofbauer cells. Lastly, we characterize the cell composition and cell-specific DNAm dynamics across gestation. Conclusions: Our results provide a comprehensive analysis of DNAm in human placental cell types from first trimester and term pregnancies. This data will serve as a useful DNAm reference for future placental studies, and we provide access to this data via download from dbGAP (phs002013.v1.p1), through interactive exploration from the web browser (https://robinsonlab.shinyapps.io/Placental_Methylome_Browser/), and through the R package planet, which allows estimation of cell composition directly from placental DNAm data.
2020-10-21 | GSE159526 | GEO
Project description:Zika virus (ZIKV) infection has caused severe unexpected clinical outcomes in neonates and adults during the recent outbreak in Latin America, particularly in Brazil. Congenital malformations associated with ZIKV have been frequently reported; nevertheless, the mechanism of vertical transmission and the involvement of placental cells remains unclear. In this study, we applied quantitative proteomics analysis in a floating explant model of chorionic villi of human placental tissues incubated with ZIKV and with ZIKV pre-adsorbed with anti-ZIKV envelope protein. The regulation of specific proteins was measured using immunofluorescence and immunoperoxidase assays. Altered levels of proteins were involved in cell proliferation, apoptosis, inflammatory processes, and the integrin-cytoskeleton complex. Antibody-opsonized ZIKV particles differentially modulated the pattern of protein expression in placental cells; this phenomenon may play a pivotal role in determining the course of infection and the role of mixed infections. These data fill gaps in our understanding of ZIKV in the placenta and help identify infection control targets.
2021-12-30 | PXD025764 | Pride
Project description:Preeclampsia is a disease of pregnant women, which is characterized by hypertension, proteinuria and chronic inflammation. There is a growing body of evidence that cause of preeclampsia lies within immunological aspect of pregnancy. This study aimed to analyze the role of CD74 in preeclampsia with a focus on its influence on communication between placental macrophages (Hofbauer cells) and trophoblasts. We have found CD74 to be highly dysregulated in preeclamptic placenta by real-time RT-PCR and Western blot methods. We identified Hofbauer cells to express the highest levels of CD74 in placenta by immunofluorescence and flow cytometry and that CD74 in preeclamptic Hofbauer cells is lower than in controls. We have performed a transcriptome analysis on human blood monocyte-derived macrophages that were non- or IL-4-activated and treated with small interfering RNA against CD74 (siRNA CD74) or non-targeting siRNA (siRNA non-targeting) as control.
2015-04-29 | E-MTAB-3309 | biostudies-arrayexpress
Project description:Pregnant women are highly susceptible to infection by the bacterial pathogen Listeria monocytogenes leading to miscarriage, premature birth, and neonatal infection. It is thought that L. monocytogenes breaches the placental barrier by infecting trophoblasts at the maternal interface. However, the fate of L. monocytogenes within the chorionic villi and how infection reaches the fetus are unsettled. Hofbauer cells (HBCs) are fetal placental macrophages and the only leukocytes residing in healthy chorionic villi, forming a last immune barrier protecting fetal blood from infection. Little is known about HBCs’ antimicrobial responses to pathogens. Here, we present the first study of L. monocytogenes interactions with human HBCs isolated from healthy term placentas. Control untreated (5 h and 24 h) HBCs, 24 h LPS/IFNgamma-stimulated, and 5 h and 24 h L. monocytogenes-infected HBCs, were lysed with TRIzol. RNA was isolated followed by on-column DNase treatment and ribo-depletion. RNA-seq libraries were made, pooled, and sequenced on an Illumina NovaSeq SP flow cell in paired-end 150 bp format to a read yield between 70 – 80 million reads (equivalent to 35 – 40 million clusters). The RNA-seq data analysis showed that HBCs undergo pro-inflammatory reprogramming upon L. monocytogenes infection and following stimulation by the potent M1-polarizing agents LPS/IFNgamma. Of particular interest, infected HBCs also upregulated genes encoding numerous pro-inflammatory chemokines known to promote placental infiltration by maternal leukocytes. However, HBCs maintained expression of a collection of tolerogenic genes accompanied by secretion of tolerogenic cytokines, consistent with their tissue homeostatic role in prevention of fetal rejection.
2021-07-27 | GSE174689 | GEO
Project description:Zika virus (ZIKV) compromises the placental integrity infecting the fetus. However, the mechanisms associated with ZIKV penetration into the placenta leading to fetal infection, are unknown. Cystatin B (CSTB), the receptor for advanced glycation end products (RAGE), and tyrosine-protein kinase receptor UFO (AXL) have been implicated in inflammation. The purpose of this work iis work aims to investigate CSTB, RAGE, and AXL receptor expression in ZIKV infected placental tissues at term. The hypothesis is that in ZIKV-infected placenta, there is overexpression of CSTB and increased inflammation affecting the RAGE and AXL receptor expression. Pathological analyses of 22 placentas were performed to determine changes caused by ZIKV infection. Quantitative proteomics, immunofluorescence, and Western Blot analysis were performed to analyze proteins and pathways affected by ZIKV infection in frozen placenta. Pathological The pathological analysis confirmed decreased size of capillaries, hyperplasia of Hofbauer cells, disruption in the trophoblasts layer, and cell agglutination associated to with ZIKV infection of placental tissue. ZIKV infection was mostly localized to the trophoblast layer. There was a significant decrease in the expression of CSTB, RAGE and AXLCSTB, RAGE and AXL expression in ZIKV positive placenta. This downregulation can impair immune responses and facilitate virus penetration into the placenta. Results are consistent with our previous studies and literature of on ZIKV infection by activation ofng Inflammasome and Pyroptosis through caspase 1 upregulation and affecting the cellular structure, tissue remodeling, and cell differentiation by upregulation of tubulin beta and heat shock protein 27.
2023-03-11 | PXD037388 | Pride
Project description:Effects of Zika virus (ZIKV) infection on placental development during pregnancy are unclear. In this study, full-term placentas from three women, each infected with ZIKV during specific pregnancy trimesters, were harvested for anatomic, immunologic and transcriptomic analysis. Each woman exhibited a unique immune response with raised IL-1RA, IP-10, EGF and RANTES expression, and neutrophil numbers during the acute infection phase. Although ZIKV NS3 antigens co-localized to placental Hofbauer cells, the placentas showed no anatomical defects. Transcriptomic analysis of samples from the placentas revealed that infection during trimester 1 caused a disparate cellular response centered on differential eIF2 signalling, mitochondrial dysfunction and oxidative phosphorylation. Despite these, the babies were delivered without any congenital anomalies. Nevertheless, these findings should translate to improve clinical prenatal screening procedures for virus-infected pregnant patients.
2019-10-22 | GSE139181 | GEO