High-throughput transcriptome-Seq and small RNA-Seq reveal novel functional genes and microRNAs for early embryonic arrest in humans

Yang, Wenmei; Lu, Zhaoyi; Zhi, Zhifu; Liu, Liling; Deng, Lingjie; Jiang, Xiaoli; Pang, Lihong

doi:10.1016/j.gene.2018.12.084

Cited by 16 publications

(12 citation statements)

References 27 publications

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“…Yang et al analyzed the villi of NP and EA patients and found that the gene expression levels of the coagulation cascade pathway were different. 22 In the MA group, the proportion of the MA value decreased, and values lower than the normal reference interval were greater, implying that either the function of platelets (or fibrinogen) was low or the platelet count (PC and fibrinogen) had decreased. Interestingly, Dankova et al found that the number of platelets in normal pregnant women was lower than that in patients who underwent abortion; however, the average fibrinogen content was higher than that in patients who underwent abortion.…”

Section: Discussionmentioning

confidence: 90%

Application of thromboelastography in diagnosing normal pregnancies and pregnancies with complications

Zhao

Cheng

Huang

et al. 2022

Clinical Laboratory Analysis

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Background This observational study aimed to compare the potential application of thromboelastography (TEG) in diagnosing women with normal pregnancy (NP) and women with threatened abortion (TA), missed abortion (MA), embryo arrest (EA), fetal death (FD), history of abnormal pregnancy (HAP), and antiphospholipid antibody syndrome (AA). Methods According to the relevant clinical criteria, patients were divided into groups, and their blood samples were subjected to TEG. Next, the parameters R, K, α‐angle, MA, LY‐30, G, and coagulation index (CI) were analyzed. Partial correlation analysis was used to analyze correlation between groups of data. LSD‐t test and Dunnett's T3 test were used to analyze continuous variables. Ordinal categorical variables were compared using ordinal logistic regression analysis and estimate odds ratio of risk factors. A receiver operating characteristic (ROC) curve was constructed to detect the ability of TEG to recognize various parameters, and areas under the curve were compared using Delong's test for diagnosing pregnancy‐related diseases. Results MA had a negative effect on the MA parameter in TEG; EA had a negative effect on the MA and G parameters; HAP had a negative effect on the CI parameter and a positive effect on the R parameter; AA had a negative effect on the CI parameter. Compared with that of the NP group, the G of the EA ( p = 0.014) group and the CI of the TA ( p = 0.036) MA ( p = 0.08) EA ( p = 0.026) HAP ( p = 0.000004) and AA ( p = 0.002) groups were reduced. In the ordinal logistic regression analysis, compared with that of the NP group, the high R value of the HAP group accounted for more than that of the NP group (OR = 48.76, p = 0.001); the high K value of the AA group accounted for more than that of the NP group (OR = 17.00, p = 0.023); the angle value distributions of the TA and AA groups were different from that of the NP group (OR = 3.30, p = 0.039; OR = 0.14, p = 0.029); the low MA value of the MA, EA, and HAP groups accounted for more than that of the NP group (OR = 0.16, p = 0.03; OR = 0.26, p = 0.005; OR = 0.11, p = 0.008); and the low CI value of the HAP group accounted for more than that of the NP group (OR = 0.09, p = 0.005). In the ROC analysis, there were no significant differences in the TEG parameters of pregnant women belonging to the NP and TA, NP and MA, NP and EA, NP and FD, NP and HAP, and NP and AA groups ( p > 0.05).

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Section: Discussionmentioning

confidence: 90%

Application of thromboelastography in diagnosing normal pregnancies and pregnancies with complications

Zhao

Cheng

Huang

et al. 2022

Clinical Laboratory Analysis

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“…No previous study has elucidated the direct role of miRNA-518 and miR-3135b in ICI. The hsa-miRNA-518 and its target gene Early growth response factor 1 ( EGR1 ) are implicated in the regulation of cell proliferation, death, and angiogenesis ( 43 ). The EGR1 serves as a pro-inflammatory factor in experimental animal models and is implicated in post-ischemic inflammation, inflammation-induced blood-brain barrier (BBB) dysfunction, and ischemic brain injury, suggesting that it plays a role in ICI progression ( 44 – 47 ).…”

Section: Discussionmentioning

confidence: 99%

“…The PPAR suppresses the expression of the pro-inflammatory factor EGR1, which is important for lipid homeostasis and inflammation ( 44 , 49 ). In a model of experimental IS, the PPARic stroke exped the (ul13) infarct volume ( 43 , 44 ). The miR-518 may play a role in the evolution of ICI by regulating PPAR and EGR1.…”

Section: Discussionmentioning

confidence: 99%

hsa-miR-518-5p/hsa-miR-3135b Regulates the REL/SOD2 Pathway in Ischemic Cerebral Infarction

Zhao

Jiang

2022

Front. Neurol.

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ObjectivesIschemic cerebral infarction (ICI) is a fatal neurovascular disorder. A bioinformatics approach based on single-cell and bulk RNA-seq analyses was applied to investigate the pathways and genes involved in ICI and study the expression profile of these genes.MethodsFirst, the aberrantly regulated “small-molecule ribonucleic acids” [microRNA (miRNAs)] and messenger RNAs (mRNAs) were analyzed using transcriptome data from the ischemic brain infarction dataset of the Gene Expression Omnibus (GEO) database. In mouse cerebrovascular monocytes, the single-cell regulatory network inference and clustering (SCENIC) workflow was used to identify key transcription factors (TFs). Then, the two miRNA-TF-mRNA interaction networks were constructed. Moreover, the molecular complex detection (MCODE) extracted the core sub-networks and identified the important TFs within these sub-networks. Finally, whole blood samples were collected for validation of the expression of critical molecules in ICI.ResultsWe identified four cell types and 266 regulons in mouse cerebrovascular monocytes using SCENIC analysis. Moreover, 112 differently expressed miRNAs and 3,780 differentially expressed mRNAs were identified. We discovered potential biomarkers in ICI by building a miRNA-TF-mRNA interaction network. The hsa-miR-518-5p/hsa-miR-3135b/REL/SOD2 was found to play a potential role in ICI progression. The expression of REL and superoxide dismutase 2 (SOD2) was significantly elevated in the ICI group in the clinical cohort (P < 0.05). Furthermore, a REL expression was elevated in endothelial cells and fibroblasts at the single-cell level, indicating that REL is a cell-specific regulon. Functional enrichment analyses revealed that REL is primarily engaged in neurotransmitter activity and oxidative phosphorylation.ConclusionsOur research uncovered novel biomarkers for ICI of neurovascular disease. The hsa-miR-518-5p/hsa-miR-3135b may regulate the REL/SOD2 pathway in ICI progression.

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“…Pregnancy loss is due to factors including uterine abnormalities, abnormal chromosomes and infection pathologies but genetic factors can also lead to a pregnancy loss (Xu et al, 2016). Transcriptomic profiles from chorionic villi of early embryonic arrest samples compared to gestation age matched elective termination samples show differentially expression in PI3K-Akt signaling pathway, Jak-STAT pathway and complement and coagulation signaling cascades (Yang et al, 2019). One study looking specifically at long non-coding RNA that are differentially regulated in chorionic villi between patients with recurrent miscarriage and those undergoing an elective abortion found up regulation of steroid hormone biosynthesis and extracellular matrix interaction and well as down regulation of TGF-beta signaling and apoptosis pathways (Wang et al, 2017).…”

Section: Early Pregnancy Lossmentioning

confidence: 99%

Functional Genomics of Healthy and Pathological Fetal Membranes

et al. 2020

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Premature preterm rupture of membranes (PPROM), rupture of fetal membranes before 37 weeks of gestation, is the leading identifiable cause of spontaneous preterm births. Often there is no obvious cause that is identified in a patient who presents with PPROM. Identifying the upstream molecular events that lead to fetal membrane weakening presents potentially actionable mechanisms which could lead to the identification of at-risk patients and to the development of new therapeutic interventions. Functional genomic studies have transformed understanding of the role of gene regulation in diverse cells and tissues involved health and disease. Here, we review the results of those studies in the context of fetal membranes. We will highlight relevant results from major coordinated functional genomics efforts and from targeted studies focused on individual cell or tissue models. Studies comparing gene expression and DNA methylation between healthy and pathological fetal membranes have found differential regulation between labor and quiescent tissue as well as in preterm births, preeclampsia, and recurrent pregnancy loss. Whole genome and exome sequencing studies have identified common and rare fetal variants associated with preterm births. However, few fetal membrane tissue studies have modeled the response to stimuli relevant to pregnancy. Fetal membranes are readily adaptable to cell culture and relevant cellular phenotypes are readily observable. For these reasons, this is now an unrealized opportunity for genomic studies isolating the effect of cell signaling cascades and mapping the fetal membrane responses that lead to PPROM and other pregnancy complications.

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High-throughput transcriptome-Seq and small RNA-Seq reveal novel functional genes and microRNAs for early embryonic arrest in humans

Cited by 16 publications

References 27 publications

Application of thromboelastography in diagnosing normal pregnancies and pregnancies with complications

Application of thromboelastography in diagnosing normal pregnancies and pregnancies with complications

hsa-miR-518-5p/hsa-miR-3135b Regulates the REL/SOD2 Pathway in Ischemic Cerebral Infarction

Functional Genomics of Healthy and Pathological Fetal Membranes

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