Immune cell profiling of preeclamptic pregnant and postpartum women by single-cell RNA sequencing
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE192693 | GEO | 2022/11/15
REPOSITORIES: GEO
Similar Datasets
Project description:Preeclampsia (PE), which affects 2-7% of human pregnancies, causes significant maternal and neonatal morbidity and mortality. To better understand the pathophysiology of PE, gene expression profiling of placental tissue from 5 controls and 5 PEs were assessed using microarray. A total of 224 transcripts were identified as being significantly differentially expressed (fold change > 2 and q value < 0.05 in the SAM software), GO enrichment analysis indicated that genes involved hypoxia, oxidative and reductive processes were significantly changed. Ten differentially expressed genes (DEGs) involved in these biological process were further verified by quantitative real-time PCR. Finally, the potential therapeutic agents for PE were explored via Connectivity Map database . In conclusion, the data obtained in this study might provide clues to better understand the pathophysiology of PE and found potential therapeutic agents for PE patients. gene expression profiling of placental tissue from 5 controls and 5 PEs were assessed using microarray.
2013-10-01 | E-GEOD-47187 | biostudies-arrayexpress
Project description:Background: Platelets may be pivotal mediators of the thrombo-haemorrhagic complications of preeclampsia (PE), linking inflammation and thrombosis with endothelial and vascular dysfunction. While gestational hypertension (GH) falls within the spectrum of hypertensive complications of pregnancy and is a risk factor for preeclampsia, it is unclear what biomarkers distinguish PE from GH. Aim: To identify specific plasma and platelet thrombo-inflammatory biomarkers indicative of preeclampsia and distinguish PE from GH. Methods: We performed multiplex immunoassays, assessed platelet and plasma proteomics and metabolomics data of PE patients, and compared with non-pregnant (NP), healthy pregnant (PC) and GH participants. Results: We report plasma proteins upregulated, enriched plasma metabolites and proteins distinctly overexpressed in platelets of PE and GH compared to NP and PC. Whilst procoagulation in PC may be fibrinogen driven, Inter-Alpha-Trypsin Inhibitors ITIH2 and ITIH3 were enriched in hypertensive complications of pregnancy (PE and GH), and fibronectin and S100A8/9 may be major procoagulant agonists in PE but not GH. In addition, platelet leucine-rich repeat-containing protein 27 and 42 (LRRC27/42) subunits of volume-regulated VRAC anion channels were markedly overexpressed in preeclampsia and may contribute to the heightened glucose sensitivity and the pro-thrombotic tendency of this disorder. Additionally, our multiplex immunoassays confirmed previous reports of increases in preeclampsia plasma cytokines, including SDF-1α, which can directly activate platelets; but also, i-309 and CTACK cytokines, whose effects on platelets we explored using STRING analysis. Conclusion: We identified biomarkers that may be monitored for preeclampsia onset and progression, and distinguish PE from GH. Also, through protein-protein interactions analysis, we generated a new hypothesis for platelets’ contribution to the thrombo-inflammatory states of preeclampsia.
2022-03-16 | PXD031278 | Pride
Project description:Background: Preeclampsia (PE) is a placental disease characterized by hypertension and proteinuria in pregnant women, which is associated with a high maternal and infantile morbidity. However, circulating biomarkers able to predict the prognosis of PE are lacking. Methods: Thirty-eight women were included in the study. They consisted of 19 patients with PE (13 with severe PE and 6 women with non-severe PE) and 19 gestational age-matched normal pregnancy controls. We measured coagulation pathway, endothelial responses and microparticle release and circulating gene expression in PE patient groups and normotensive controls. Results: The measurement of markers associated with coagulation pathway, endothelial activation and circulating microparticles enabled to discriminate PE from normal pregnancy but were not sufficient to distinguish severe from non-severe PE. PE patients also exhibited a specific transcriptional program distinct from that of control women and subtle differences were observed between severe and non-severe PE. Functional annotation of the up-modulated signature in PE highlighted two main functions related to ribosome and complement. Importantly, we found that 8 genes were specifically up-modulated in severe preeclampsia. Among these genes, the expression of VSIG4 was significantly increased in patients with severe preeclampsia in comparison with controls and patients with non-severe preeclampsia. Conclusion: Using transcriptional signatures of blood samples, we identified the gene encoding the estrogen receptor as a potential diagnostic marker of severe preeclampsia. In addition, the determination of this gene may improve the prognostic assessment of severe preeclampsia.
2014-05-14 | GSE48424 | GEO
Project description:Intercellular communication via extracellular vesicles (EVs) is a highly dynamic and specific process. The interaction between EVs and their target cells, especially immune cells, results in functional and phenotype changes that consequently may play a significant role in various physiological states and the pathogenesis of immune-mediated disorders. Monocytes are the most prominent environment sensing immune cells in circulation, skilled to shape their microenvironments via cytokine secretion and further differentiation. Both the circulating monocyte subset distribution and the blood plasma EV pattern are characteristic for preeclampsia, a pregnancy induced immune-mediated hypertensive disorder. We hypothesized that preeclampsia-associated EVs (PE-EVs) induced functional and phenotypic alterations of monocytes. First we proved EV binding and uptake by THP-1 cells. Cellular origin and protein cargo of circulating PE-EVs were characterized by flow cytometry and mass spectrometry. An altered phagocytosis-associated molecular pattern was found on PE-EVs: an elevated CD47 “don’t eat me” signal and decreased exofacial phosphatidylserine “eat-me” signal were found along with decreased uptake of PE-EVs. PE-EVs induced significantly lower chemotaxis and cell motility, but accelerated cell adhesion of THP-1 cells. PE-EVs caused sustained TNF production of THP-1 cells. PE-EVs induced altered monocyte functions suggest that circulating PE-EVs may have a role in the pathogenesis of preeclampsia.
2018-04-09 | PXD008665 | Pride
Project description:Maternal serum levels of calcyclin and heat shock protein 90 were compared throughout pregnancy from the first trimester till term among women with preeclampsia (PE) and age-matched normotensive pregnant controls (C). Serum samples from two different studies, a nested case-control study embedded in the Rotterdam periconception cohort and the Lepra Study both conducted at the Erasmus MC in Rotterdam. They were collected in the first, second and third trimester of pregnancy in 43 patients with preeclampsia, consisting of 20 early-onset and 23 late-onset preeclampsia, and 46 normotensive pregnant controls. A serum based 2D LC-MS assay on Parallel Reaction Monitoring mode using a high resolution tribrid mass spectrometer was used to quantify both calcyclin and heat shock protein 90.
2018-11-21 | PXD009025 | Pride
Project description:Background: Preeclampsia, a pregnancy complication with hypertension and proteinuria, seriously threats the health and lives of the mother and the baby. The role of peripheral natural killer cells (NK cells) in the pre-eclampsia is unclear. Methods: Flow cytometry was performed to detect the expression of CD158a (KIR2DL1) and CD158b (KIR2DL2/3) in peripheral NK cells of non-pregnant healthy women (HW), healthy pregnant women (HP), and patients with pre-eclampsia (PE). Differentially expressed genes (DEGs) in CD158a+ and CD158b+ NK cells were identified by RNA-sequencing and real-time PCR. Protein array analysis was used to identify altered protein levels in the serum of study participants. Findings: CD158a+ NK cell numbers were significantly increased in the peripheral blood of patients with pre-eclampsia while the number of CD158b+ NK cells was significantly reduced. The percentage of CD158a+ NK cells was positively correlated with systolic blood pressure while the percentage of CD158b+ NK cells was negatively correlated with systolic blood pressure. RNA-seq and real-time PCR showed that the expression of ERAP2 and GCH1, the genes that regulate blood pressure and angiogenesis, was decreased in CD158a+ compared to CD158b+ NK cells. Interpretation: CD158a+ and CD158b+ NK cell numbers are altered in the peripheral blood of patients with pre-eclampsia compared to healthy individuals, which is associated with the increase in blood pressure.
2021-11-22 | GSE189237 | GEO
Project description:Background: Preeclampsia (PE) is a placental disease characterized by hypertension and proteinuria in pregnant women, which is associated with a high maternal and infantile morbidity. However, circulating biomarkers able to predict the prognosis of PE are lacking. Methods: Thirty-eight women were included in the study. They consisted of 19 patients with PE (13 with severe PE and 6 women with non-severe PE) and 19 gestational age-matched normal pregnancy controls. We measured coagulation pathway, endothelial responses and microparticle release and circulating gene expression in PE patient groups and normotensive controls. Results: The measurement of markers associated with coagulation pathway, endothelial activation and circulating microparticles enabled to discriminate PE from normal pregnancy but were not sufficient to distinguish severe from non-severe PE. PE patients also exhibited a specific transcriptional program distinct from that of control women and subtle differences were observed between severe and non-severe PE. Functional annotation of the up-modulated signature in PE highlighted two main functions related to ribosome and complement. Importantly, we found that 8 genes were specifically up-modulated in severe preeclampsia. Among these genes, the expression of VSIG4 was significantly increased in patients with severe preeclampsia in comparison with controls and patients with non-severe preeclampsia. Conclusion: Using transcriptional signatures of blood samples, we identified the gene encoding the estrogen receptor as a potential diagnostic marker of severe preeclampsia. In addition, the determination of this gene may improve the prognostic assessment of severe preeclampsia. Thirty-eight women were included in the study: 19 patients with PE, including 6 women with non-severe PE and 13 with severe PE, and 19 women with normal pregnancy (NP) selected according to age, weight, smoking status, race, gestational age at the inclusion, and blood pH (Table 1 of manuscript). Women with NP had no history of medical illness or medication, and received routing prenatal care. The diagnostic of PE was based on a blood pressure of M-bM-^IM-% 140/90 mmHg taken twice, uricemia above normal laboratory range (120-420 M-BM-5mol/L), and proteinuria higher than 300 mg in a 24 hour-collection, occurring after 20 gestational weeks in previously normotensive women (Table 2). The criteria used to define severe PE included one of the following conditions: a blood pressure higher than 160/110 mmHg, a proteinuria higher than 1500 mg/24h), a multisystem disorder, maternal cerebral symptoms (seizures, stroke) or intrauterine growth restriction below the 3M-BM-0 percentile. Women with multiple gestations, fetal congenital malformations/chromosomal abnormalities, recent infection, antiphospholipid antibodies, trauma, drug or alcohol abuse during pregnancy, preexisting hypertension, thrombophilia with PE history, or women receiving anticoagulant or antiaggregation therapy were excluded from the study. Two microarrays (one non-severe PE and one normal) were discarded from the analysis for technical reasons. Thus, only 36 microarrays are included here.
2014-05-14 | E-GEOD-48424 | biostudies-arrayexpress
Project description:Preeclampsia (PE), which affects 2-7% of human pregnancies, causes significant maternal and neonatal morbidity and mortality. To better understand the pathophysiology of PE, gene expression profiling of placental tissue from 5 controls and 5 PEs were assessed using microarray. A total of 224 transcripts were identified as being significantly differentially expressed (fold change > 2 and q value < 0.05 in the SAM software), GO enrichment analysis indicated that genes involved hypoxia, oxidative and reductive processes were significantly changed. Ten differentially expressed genes (DEGs) involved in these biological process were further verified by quantitative real-time PCR. Finally, the potential therapeutic agents for PE were explored via Connectivity Map database . In conclusion, the data obtained in this study might provide clues to better understand the pathophysiology of PE and found potential therapeutic agents for PE patients.
2013-10-01 | GSE47187 | GEO
Project description:Defective deep placentation, an abnormal transformation of the spiral arteries in the junctional zone of the myometrium, is known to cause significant obstetrical complications such as preeclampsia (PE), fetal growth restriction, and placental infarcts with fetal death. Serological biomarkers to predict and diagnose PE would help antenatal care and reduce the obstetrical complications. To discover biomarkers for prediction of PE, we first performed global proteome profiling of three pairs of maternal plasma samples obtained from the early second trimester pregnant women who subsequently developed PE and controls to identify proteins that were abundant in the patients. We further evaluated the expression changes of PE representing proteins in stored plasma samples of a cohort of subsequently developed PE and their matched controls by MRM assay. We identified both Complement C1s subcomponent (p-value = 0.041) and Protein AMBP (p-value = 0.043) were up-regulated in the cohort of PE plasma samples before manifestation of clinical disease. We propose that these proteins may be involved in the remodeling process of the spiral arteries even before the manifestation of PE. These proteins could be served as potential plasma biomarkers to predict pregnant women at increased risk of developing PE.
2018-07-05 | PXD003419 | Pride