scholarly journals Integrated analysis of long non-coding RNA and mRNA expression in endometrial stromal cells induced by poly (I:C) identifies immune response genes

2020 ◽  
Author(s):  
Ming Zhang ◽  
Yan Zhang ◽  
Qiuying Wu ◽  
Ling Xu ◽  
Yutian Zeng ◽  
...  
Keyword(s):  
Immune Response ◽  
Virus Infection ◽  
Signaling Pathways ◽  
Expression Analysis ◽  
Stromal Cells ◽  
Noncoding Rna ◽  
Expression Profiles ◽  
Poly I:C ◽  
Integrated Analysis ◽  
Endometrial Stromal Cells

Abstract Background The uterus of an animal is relatively easily infected by pathogenic microorganisms, which can cause serious reproductive disorders and economic loss to animal husbandry. The presence of long noncoding RNA (lncRNA) is closely related to many diseases. Poly(I:C) is a synthetic double-stranded RNA that is often used as a substitute for dsRNA viral infection. In this study, we analyzed the mRNA and lncRNA expression profiles of in vitro cultured rabbit endometrial stromal cells (ESCs) after poly(I:C)-induction, to explore the role of these RNAs in the immune response. Results We identified 10,927 lncRNAs and 20,494 mRNAs, of which 291 lncRNAs and 1311 mRNAs were significantly differentially expressed (DE) between the control and poly(I:C) groups ( p <0.05). GO and KEGG analysis showed that DE genes and target genes of DE lncRNAs were enriched in relation to the occurrence of various diseases, development of tissues and organs, metabolic processes, and the immune response. Moreover, these genes were also enriched in many pathways related to immune and inflammatory responses, such as the toll-like receptor and the NF-κB and Jak-STAT signaling pathways. Co-expression analysis of lncRNA and mRNA revealed that there were significant relationships between a number of lncRNAs including MSTRG.153189.1, MSTRG.102664.8, MSTRG.39626.1, MSTRG.68469.1, MSTRG.137189.4, MSTRG.32118.5 and MSTRG.76080.1, and the immune system genes, CCL2, CCL5, IL-1, IL-6, IFN and ISG15, which suggested that lncRNAs in ESCs might be involved in regulation of the immune response to poly(I:C) through genes related to immune signaling pathways. Conclusions Our results provide both transcriptomic and epigenetic insights into the immune response of uterine cells to dsRNA virus infection. Comprehensive lncRNA and mRNA transcriptomes in rabbit ESCs exposed to poly(I:C) were profiled. Co-expression analysis identified an integrated lncRNA-mRNA interaction network, implying that key genes or lncRNAs exerted critical influences on the immune response to virus infection.

scholarly journals Shp2 in uterine stromal cells critically regulates on time embryo implantation and stromal decidualization by multiple pathways during early pregnancy

PLoS Genetics ◽  
2022 ◽  
Vol 18 (1) ◽  
pp. e1010018
Author(s):  
Jianghong Cheng ◽  
Jia Liang ◽  
Yingzhe Li ◽  
Xia Gao ◽  
Mengjun Ji ◽  
...  
Keyword(s):  
Gene Expression ◽  
Signaling Pathways ◽  
Stromal Cells ◽  
Embryo Implantation ◽  
Endometrial Stromal Cells ◽  
Conditional Deletion ◽  
Enhancer Binding Protein ◽  
Epithelial Remodeling ◽  
Multiple Signaling ◽  
Transcription 3

Approximately 75% of failed pregnancies are considered to be due to embryo implantation failure or defects. Nevertheless, the explicit signaling mechanisms governing this process have not yet been elucidated. Here, we found that conditional deletion of the Shp2 gene in mouse uterine stromal cells deferred embryo implantation and inhibited the decidualization of stromal cells, which led to embryonic developmental delay and to the death of numerous embryos mid-gestation, ultimately reducing female fertility. The absence of Shp2 in stromal cells increased the proliferation of endometrial epithelial cells, thereby disturbing endometrial epithelial remodeling. However, Shp2 deletion impaired the proliferation and polyploidization of stromal cells, which are distinct characteristics of decidualization. In human endometrial stromal cells (hESCs), Shp2 expression gradually increased during the decidualization process. Knockout of Shp2 blocked the decidual differentiation of hESCs, while Shp2 overexpression had the opposite effect. Shp2 knockout inhibited the proliferation of hESCs during decidualization. Whole gene expression profiling analysis of hESCs during the decidualization process showed that Shp2 deficiency disrupted many signaling transduction pathways and gene expression. Analyses of hESCs and mouse uterine tissues confirmed that the signaling pathways extracellular regulated protein kinases (ERK), protein kinase B (AKT), signal transducer and activator of transcription 3 (STAT3) and their downstream transcription factors CCAAT/enhancer binding protein β (C/EBPβ) and Forkhead box transcription factor O1 (FOXO-1) were involved in the Shp2 regulation of decidualization. In summary, these results demonstrate that Shp2 plays a crucial role in stromal decidualization by mediating and coordinating multiple signaling pathways in uterine stromal cells. Our discovery possibly provides a novel key regulator of embryo implantation and novel therapeutic target for pregnancy failure.

scholarly journals Loss of imprinting control of the lncRNA H19-fetal mitogen IGF2 gene cluster in the decidual microenvironment of patients with idiopathic spontaneous miscarriages

2021 ◽  
Author(s):  
Xue Wen ◽  
Qi Zhang ◽  
Lei Zhou ◽  
Zhaozhi Li ◽  
Xue Wei ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Noncoding Rna ◽  
Recurrent Miscarriage ◽  
Critical Role ◽  
Ctcf Binding ◽  
Ctcf Binding Site ◽  
Monoallelic Expression ◽  
Endometrial Stromal Cells ◽  
Control Center ◽  
Loss Of Imprinting

Abstract Miscarriage, the spontaneous loss of a pregnancy before the fetus achieves viability, is a common complication of pregnancy. Decidualization plays a critical role in the implantation of the embryo. To search for molecular factors underlying miscarriage, we explored the role of long noncoding RNAs (lncRNAs) in the decidual microenvironment, where the molecular crosstalk at the feto–maternal interface occurs. By integrating RNA-seq data from recurrent miscarriage patients and decidualized endometrial stromal cells, we identified H19 , a noncoding RNA that exhibits paternally imprinted monoallelic expression in normal tissues, as the most upregulated lncRNA associated with miscarriage. Aberrant upregulation of H19 lncRNA was observed in decidual tissues derived from patients with spontaneous miscarriage as well as decidualized endometrial stromal cells. The maternally imprinted fetal mitogen Igf2, which is usually reciprocally co-regulated with H19 in the same imprinting cluster, was also upregulated. Notably, both genes underwent loss of imprinting, as H19 and IGF2 were actively transcribed from both parental alleles in decidual tissues. Mechanistically, this loss of imprinting in decidual tissues was associated with the loss of the H3K27m3 suppression marker in the IGF2 promoter, CpG hypomethylation at the central CTCF binding site in the imprinting control center (ICR) that is located between IGF2 and H19 , and the loss of CTCF-mediated intrachromosomal looping. These data provide the first evidence that aberrant control of the ICR epigenotype-intrachromosomal looping- H19/IGF2 imprinting pathway may be a critical epigenetic risk factor in the abnormal decidualization related to miscarriage.

scholarly journals Integrated Analysis of LncRNA-mRNA Coexpression in the Extracellular Matrix of Developing Deciduous Teeth in Miniature Pigs

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Yang Li ◽  
Guoqing Li ◽  
Fu Wang ◽  
Xiaoshan Wu ◽  
Zhifang Wu ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Noncoding Rna ◽  
Tooth Development ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Deciduous Teeth ◽  
Human Tooth ◽  
Integrated Analysis ◽  
Miniature Pigs ◽  
Tooth Germs

Miniature pigs, a valuable alternative model for understanding human tooth development, have deciduous teeth from all four tooth families that are replaced once by permanent molars. The extracellular matrix (ECM) supports cells and maintains the integrity of tooth germs during tooth development. However, details on the role of the ECM in tooth development are poorly understood. Here, we performed long noncoding RNA (lncRNA) and messenger RNA (mRNA) expression profiles in the ECM components of deciduous tooth germs by RNA sequencing in miniature pigs. From the early cap to the late bell stages, we identified 4,562 and 3,238 differentially expressed genes (DEGs) from E40 to E50 and E50 to E60, respectively. In addition, a total of 1,464 differentially expressed lncRNAs from E40 to E50 and 969 differentially expressed lncRNAs from E50 to E60 were obtained. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that DEGs were enriched significantly for multiple signaling pathways, especially for the ECM pathway. We then outlined the detailed dynamic gene expression profiling of ECM components during deciduous molar development. Comparison of the cap and bell stages revealed that the structure and functions of the ECM dynamically changed. The ECM-related genes, including THBS1, COL4A5, COL4A6, COL1A1, CHAD, TNR, GP1BA, and ITGA3, were significantly changed, and some were shown to enrich during the bell stage development. Finally, we outlined the coexpression of lncRNAs and ECM properties during tooth development. We showed that the interplay of key lncRNAs could change ECM processes and influence the ECM establishment of tooth patterns to accomplish full tooth formation. These results might provide information to elucidate the regulation network of the lncRNA and ECM in tooth development.

scholarly journals Hypoxia-Induced MicroRNA-20a Expression Increases ERK Phosphorylation and Angiogenic Gene Expression in Endometriotic Stromal Cells

2012 ◽  
Vol 97 (8) ◽  
pp. E1515-E1523 ◽  
Author(s):  
Shih-Chieh Lin ◽  
Chih-Chuan Wang ◽  
Meng-Hsing Wu ◽  
Shang-Hsun Yang ◽  
Yo-Hua Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stromal Cells ◽  
Noncoding Rna ◽  
Hypoxia Inducible Factor ◽  
Transcriptional Response ◽  
Fine Tuning ◽  
Translational Efficiency ◽  
Endometrial Stromal Cells ◽  
Small Noncoding Rna ◽  
Erk Phosphorylation

Abstract Context: Aberrant activation of MAPK has been implicated to play important roles in pathological processes of endometriosis. However, how MAPK are constitutively activated in endometriotic tissues remains largely unknown. microRNA are small noncoding RNA that regulate the stability or translational efficiency of target mRNA by interacting with the 3′ untranslated region. Thus, miRNA are thought to be modulators of the transcriptional response, fine-tuning gene expression. Objective: The aim of this study was to evaluate the functional roles of microRNA-20a (miR20a) in MAPK activation and the pathogenesis of endometriosis. Design: miR20a expression was analyzed in nonpaired (endometrium = 17; endometriosis = 37) and paired (n = 12) endometriotic tissues by quantitative RT-PCR. Overexpression of miR20a in eutopic endometrial stromal cells or inhibition of miR20a in ectopic endometriotic stromal cells was used to evaluate its impact on ERK phosphorylation and subsequently angiogenesis- and proliferation-related gene expression. Results: Levels of miR20a were up-regulated in endometriotic stromal cells. Elevation of miR20a was up-regulated by hypoxia inducible factor-1α. The up-regulation of miR20a causes the down-regulation of dual-specificity phosphatase-2, which leads to prolonged ERK phosphorylation and an increase in the expression of several angiogenic genes. Furthermore, the up-regulation of miR20a enhances the prostaglandin E2-induced expression of fibroblast growth factor-9, a potent mitogen that stimulates both endothelial and endometrial cell proliferation. Conclusion: Our findings provide the novel mechanism that not only functionally links together hypoxic stress, miR20a expression, aberrant ERK phosphorylation, and angiogenesis but also demonstrates that miR20a is an important modulator in the development of endometriosis.

scholarly journals GATA2 and Progesterone Receptor Interaction in Endometrial Stromal Cells Undergoing Decidualization

Endocrinology ◽  
2020 ◽  
Vol 161 (6) ◽  
Author(s):  
Amanda Kohlmeier ◽  
Christia Angela M Sison ◽  
Bahar D Yilmaz ◽  
John S Coon V ◽  
Matthew T Dyson ◽  
...  
Keyword(s):  
Progesterone Receptor ◽  
Early Pregnancy ◽  
Stromal Cells ◽  
Expression Profiles ◽  
Stem Cell Differentiation ◽  
Receptor Interaction ◽  
Rna Seq ◽  
Endometrial Stromal Cells ◽  
Endometrial Cells ◽  
Binding Regions

Abstract The transcription factor GATA2 is important for endometrial stromal cell decidualization in early pregnancy. Progesterone receptor (PGR) is also critical during decidualization but its interaction with GATA2 in regulating genes and pathways necessary for decidualization in human endometrium are unclear. RNA-sequencing (RNA-seq) was performed to compare gene expression profiles (n = 3), and chromatin immunoprecipitation followed by sequencing (ChIP-seq) using an antibody against GATA2 (n = 2) was performed to examine binding to target genes in human endometrial stromal cells undergoing in vitro decidualization (IVD including estrogen, progestin, and 3′,5′-cyclic AMP analogue) or vehicle treatment. We identified 1232 differentially expressed genes (DEGs) in IVD vs vehicle. GATA2 cistrome in IVD-treated cells was enriched with motifs for GATA, ATF, and JUN, and gene ontology analysis of GATA2 cistrome revealed pathways that regulate cholesterol storage, p38 mitogen-activated protein kinase, and the c-Jun N-terminal kinase cascades. Integration of RNA-seq and ChIP-seq data revealed that the PGR motif is highly enriched at GATA2 binding regions surrounding upregulated genes in IVD-treated cells. The integration of a mined public PGR cistrome in IVD-treated human endometrial cells with our GATA2 cistrome showed that GATA2 binding was significantly enhanced at PGR-binding regions in IVD vs vehicle. Interrogating 2 separate ChIP-seq data sets together with RNA-seq revealed integration of GATA2 and PGR action to coregulate biologic processes during decidualization of human endometrial stromal cells, specifically via WNT activation and stem cell differentiation pathways. These findings reveal the key pathways that are coactivated by GATA2 and PGR that may be therapeutic targets for supporting implantation and early pregnancy.

scholarly journals Micro-Transcriptome Analysis Reveals Immune-Related MicroRNA Regulatory Networks of Paralichthys olivaceus Induced by Vibrio anguillarum Infection

2020 ◽  
Vol 21 (12) ◽  
pp. 4252
Author(s):  
Xianhui Ning ◽  
Li Sun
Keyword(s):  
Immune Response ◽  
Transcriptome Analysis ◽  
Regulatory Networks ◽  
Expression Profiles ◽  
Paralichthys Olivaceus ◽  
Vibrio Anguillarum ◽  
Japanese Flounder ◽  
Integrated Analysis ◽  
Immune Gene ◽  
Hub Genes

MicroRNAs (miRNAs) are non-coding regulatory RNAs that play a vital part in the host immune response to pathogen infection. Japanese flounder (Paralichthys olivaceus) is an important aquaculture fish species that has suffered from bacterial diseases, including that caused by Vibrio anguillarum infection. In a previous study, we examined the messenger RNA (mRNA) expression profiles of flounder during V. anguillarum infection and identified 26 hub genes in the flounder immune response. In this study, we performed the micro-transcriptome analysis of flounder spleen in response to V. anguillarum infection at 3 different time points. Approximately 277 million reads were obtained, from which 1218 miRNAs were identified, including 740 known miRNAs and 478 novel miRNAs. Among the miRNAs, 206 were differentially expressed miRNAs (DEmiRs), and 104 of the 206 DEmiRs are novel miRNAs identified for the first time. Most of the DEmiRs were strongly time-dependent. A total of 1355 putative target genes of the DEmiRs (named DETGs) were identified based on integrated analysis of miRNA-mRNA expressions. The DETGs were enriched in multiple functional categories associated with immunity. Thirteen key DEmiRs and 66 immune DETGs formed an intricate regulatory network constituting 106 pairs of miRNAs and DETGs that span five immune pathways. Furthermore, seven of the previously identified hub genes were found to be targeted by 73 DEmiRs, and together they formed interlinking regulatory networks. These results indicate that V. anguillarum infection induces complicated miRNA response with extensive influences on immune gene expression in Japanese flounder.

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