Transgenic expression of human C19MC miRNAs impacts placental morphogenesis
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE141131 | GEO | 2019/11/28
REPOSITORIES: GEO
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Project description:Transgenic expression of human C19MC miRNAs impacts placental morphogenesis
| PRJNA592184 | ENA
Project description:Analyze miRNA expression levels in HTR-8/SVeo cells stably transfected with a BAC plasmid containing the entire C19MC miRNA cluster HTR-8/SVeo cells were transfected with a modified BAC plasmid containing the entire C19MC miRNA cluster and carrying a zeocin selection cassette. Several independent clones and a mixed population of transfected cells were analyzed and compared to non-transfected HTR-8/SVeo cells and primary human trophoblasts that express the C19MC miRNAs endogenously
2014-04-08 | E-GEOD-56562 | biostudies-arrayexpress
Project description:Analyze gene expression profiles in HTR-8/SVeo cells stably transfected with a BAC plasmid containing the entire C19MC miRNA cluster HTR-8/SVeo cells were transfected with a modified BAC plasmid containing the entire C19MC miRNA cluster and carrying a zeocin selection cassette. Several independent clones and a mixed population of transfected cells were analyzed and compared to non-transfected HTR-8/SVeo cells and primary human trophoblasts that express the C19MC miRNAs endogenously
2014-04-08 | E-GEOD-56564 | biostudies-arrayexpress
Project description:IntroductionThe chromosome 19 miRNA cluster (C19MC) encodes a large family of microRNAs (miRNAs) that are abundantly expressed in the placenta of higher primates and also in certain cancers. In the placenta, miRNAs from this cluster account for nearly 40% of all miRNAs present in trophoblasts. However, the function of these miRNAs in the placenta remains poorly understood. Recent observations reveal a role for these miRNAs in cell migration, and suggest that they are involved in the development and function of the human placenta. Here, we examine the placenta in transgenic mice expressing the human C19MC miRNAs.MethodsWe produced transgenic mice using pronuclear microinjection of a bacterial artificial chromosome plasmid carrying the entire human C19MC locus and derived a homozygous line using crossbreeding. We performed morphological characterization and profiled gene expression changes in the placentas of the transgenic mice.ResultsC19MC transgenic mice delivered on time with no gross malformations. The placentas of transgenic mice expressed C19MC miRNAs and were larger than wild type placentas. Histologically, we found that the transgenic placenta exhibited projections of spongiotrophoblasts that penetrated deep into the labyrinth. Gene expression analysis revealed alterations in the expression of several genes involved in cell migration, with evidence of enhanced cell proliferation.DiscussionMice that were humanized for transgenically overexpressed C19MC miRNAs exhibit enlarged placentas with aberrant delineation of cell layers. The observed phenotype and the related gene expression changes suggest disrupted migration of placental cell subpopulations.
| S-EPMC7595355 | biostudies-literature
Project description:Induced expression of the C19MC miRNAs in HTR-8/SVneo cells
| PRJNA243912 | ENA
Project description:Analyze gene expression profiles in HTR-8/SVeo cells stably transfected with a BAC plasmid containing the entire C19MC miRNA cluster
2014-04-08 | GSE56564 | GEO
Project description:Analyze miRNA expression levels in HTR-8/SVeo cells stably transfected with a BAC plasmid containing the entire C19MC miRNA cluster
2014-04-08 | GSE56562 | GEO
Project description:B cell chronic lymphocytic leukemia (CLL) is often preceded by a benign monoclonal or oligoclonal CD5+ B cell lymphocytosis. We have generated transgenic mice expressing a catalytically inactive, dominant-negative recombination activating gene 1 (dnRAG1 mice) in the periphery. These animals develop an early-onset indolent CD5+ B cell lymphocytosis, caused in part by a defect in secondary V(D)J rearrangements initiated to alter autoreactive B cell receptor specificity. Hypothesizing that the CD5+ B cells accumulating in dnRAG1 mice represent a CLL precursor, we crossed dnRAG1 mice with CLL-prone Eµ-TCL1 mice to determine whether dnRAG1 expression in Eµ-TCL1 mice accelerates the onset of CLL-like disease. We find that CD5+ B cell expansion and CLL progression occurs more rapidly and uniformly in double-transgenic mice (DTG mice) compared to Eµ-TCL1 mice, but with similar phenotypic and leukemogenic features. To gain insight into genes or pathways responsible for CD5+ B cell accumulation in the transgenic mice, we performed comparative gene expression profiling studies using normal and CD5+ B cells isolated from wild-type and transgenic mice at either 12 weeks of age (pre-leukemia) or at CLL onset in DTG mice (using age-matched wild-type and single-transgenic mice as controls). These analyses confirm the upregulation of tolerogenic genes in CD5+ B cells and reveal a possible role for prolactin signaling in the regulation of receptor editing. This study suggests that a failure to remodel B cell antigen receptor genes in response to autoreactivity may promote the benign accumulation of CD5+ B cells, which may then be subjected to secondary genetic lesions that promote CLL progression. dnRAG1 mice were bred to Eµ-TCL1 mice to obtain cohorts of wild-type (WT), single-transgenic (dnRAG1 and Eµ-TCL1), and DTG mice. Splenic CD19+B220hiCD5- B cells from WT mice or CD19+CD5+ B cells from transgenic mice were purified using fluorescence activated cell sorting (FACS). Biotin end-labeled cDNA prepared from the sorted cells was hybridized to Mouse Gene 1.0 ST Arrays. These experiments were performed two independent times: once with a cohort of 12-week-old mice, and once with older mice (>34 weeks old) consisting of two ill DTG mice and their age-matched counterparts. At least two biological replicates were used where possible.
2013-06-04 | E-GEOD-44940 | biostudies-arrayexpress
Project description:microRNAs are increasingly seen as important regulators of placental development and opportunistic biomarker targets. We generated miRNA profiles using 96 placentas from presumed normal pregnancies, across early gestation, in combination with matched profiles from maternal plasma. We identified 637 miRNAs with expression in 86 samples (after removing poor quality samples), showing a clear gestational age gradient and identified 374 differentially expressed (DE) miRNAs across a gestational cut-off of 6-10 weeks’ and 11-23 weeks’. We see a clear gestational age group bias in miRNA clusters C19MC, C14MC, miR-17~92 and paralogs, regions that also include many DE miRNAs. Proportional change in expression of placenta-specific miRNA clusters was reflected in maternal plasma, with C19MC miRNAs miR-516b-5p and 517a-3p showing potential as a biomarkers. Chorionic villous samples across early gestation display differential miRNA profiles, particularly in the expression of highly placenta-specific miRNA clusters, and at the presumed introduction of oxygenated maternal blood into the placenta. Data presented here comprise a clinically important reference set for studying early placenta development and enabling development of minimally invasive methods for monitoring placental health.
2021-12-23 | GSE151362 | GEO
Project description:Although recent studies have revealed that microRNAs (miRNAs) regulate fundamental Natural Killer (NK) cell processes including cytotoxicity and cytokine production, little is known about the miRNA-gene regulatory relationships in maternal peripheral blood NK (pNK) cells during pregnancy. To predict the role of miRNAs within gene regulatory networks of maternal pNK cells during pregnancy, we performed comprehensive miRNA and gene expression profiling of maternal pNK cells using a combination of real-time PCR-based array and DNA microarray analyses and analyzed these differential expression levels between first- and third-trimester pNK cells. Furthermore, we constructed regulatory networks for miRNA-mediated gene expression in pNK cells during pregnancy by Ingenuity Pathway Analysis. By PCR-based array analysis of miRNAs, 12 miRNAs including 6 placenta-derived miRNAs [chromosome 19 microRNA cluster (C19MC) miRNAs] were significantly upregulated in third-trimester pNK cells compared to first-trimester pNK cells. pNK cells incorporated C19MC miRNAs, whose interaction would be mediated via exosomes. Rapid clearance of C19MC miRNAs also occurred in NK cells after delivery. By DNA microarray analysis, 13 NK cell function-related genes were significantly downregulated between first- and third-trimester pNK cells. By pathway and network analysis, 9 downregulated NK-function-associated genes were in silico target candidates of 12 upregulated miRNAs including C19MC miRNA miR-512-3p. The results suggest that transfer of placental C19MC-miRNAs into maternal pNK cells occurs during pregnancy. The present study provides clues to understand maternal NK cell functions Gene expressions in human maternal peripheral blood NK cells were measured at 1st-trimester, 3rd-trimester. Five independent experiments were performed at each term (1st-trimester or 3rd-trimester) using different donors for each experiment.
2015-01-13 | E-GEOD-64884 | biostudies-arrayexpress