Project description:MicroRNA ablation prevents multiciliogenesis via cell cycle deregulation MicroRNAs (miRNAs) have been implicated in various biological processes but have been most frequently described to inhibit proliferation and tumorigenesis. Here we describe an essential function of the miR-34/449 family during differentiation of multiciliated cells that is mediated by their well-described suppression of cell cycle progression. Constitutive deletion of all six members of this miRNA family triggers a derepression of multiple cell cycle-promoting proteins, thereby preventing epithelial cells from exiting the cell cycle and to maintain in a quiescent state. As a result, formation of motile multicilia is strongly inhibited in several tissues including the respiratory epithelium and the fallopian tube. Consequently, mice lacking miR-34/449 genes display infertility as well as severe chronic airway disease leading to postnatal death. These results show how miRNA-mediated repression of the cell cycle is required to allow multiciliogenesis to proceed during epithelial differentiation.
Project description:We used microarrays to detail the global programme of gene expression that occurs in response to miR-449 or miR-34 overexpression in proliferating HAECs.
Project description:We used microarrays to detail the global programme of gene expression that occurs in response to miR-449 or miR-34 overexpression in proliferating HAECs. Each donors were transfected with pre-miR-Negative control, pre-miR-449a and pre-miR-449b. The donors 3 and 4 were morever transfected with pre-miRs-34 (34a, 34b-5p, 34c-5p).
Project description:In this study, we comparatively analyzed the members of the miR-449 family (miR-449a, miR-449b, and miR-449c) with regards to their target genes and functional effects in hepatocellular carcinoma (HCC). Microarray analysis after transient transfection of miR-449a, miR-449b, and/or miR-449c in the HCC cell line HLE identified putative target genes of miR-449a, miR-449b, and miR-449c.
Project description:In this study, we comparatively analyzed the members of the miR-449 family (miR-449a, miR-449b, and miR-449c) with regards to their target genes and functional effects in hepatocellular carcinoma (HCC). Microarray analysis after transient transfection of miR-449a, miR-449b, and/or miR-449c in the HCC cell line HLE identified putative target genes of miR-449a, miR-449b, and miR-449c. For transient overexpression of miRNAs, the HCC cell line HLE was transfected with 50 nM Allstars Negative Control or miScript miRNA mimics. MiRNA mimics for miR-449a, miR-449b, and miR-449c were either single transfected or cotransfected in equimolar amounts (16.7 nM each). Global mRNA expression profiling was performed utilizing pooled RNA of three biological replicates per microarray and two microarrays per condition.
Project description:Analysis of gene expression (mRNA profiles) from mouse pachytene cells. Mir-34bc+/-;449+/- samples are compared against mir-34bc-/-;449-/- samples .
Project description:This SuperSeries is composed of the following subset Series: GSE22141: MicroRNA signature during the time course of regeneration of the human airway mucociliary epithelium GSE22142: Transcriptome analysis during the time course of regeneration of the human airway mucociliary epithelium GSE22143: Transcriptomic impact of microRNAs-449 or microRNAs-34 overexpression in proliferating human airway epithelial cells GSE22144: miRNAs high throughput sequencing profiling of regenerating human airway epithelial cells GSE22145: miRNAs high throughput sequencing profiling of basals cells and columnar cells GSE22146: microRNAs signatures of Xenopus laevis embryo epidermis at stage 11 (non ciliated) and 26 (ciliated) using high throughput sequencing Refer to individual Series
Project description:We have combined high-quality genome sequencing and RNA-sequencing data within a 17-individual, three generation family. Using these data, we have contrasted cis-acting expression, allele-specific expression and splicing quantitative trait loci (collectively termed eQTLs) within the family to eQTLs discovered within a cell-type and ethnicity-matched population sample. We identified that eQTL that exhibit larger effects in the family compared to the population are enriched for rare regulatory and splicing variants and were more likely to influence essential genes. In addition, we identify several large effect-size eQTLs within the family for genes involved in complex disease. Through analysis of eQTLs in a large family we also report the utility of non-coding genome annotation to predicting the effect of rare non-coding variants. We find that a combination of distance to the transcription start site, evolutionary constraint and epigenetic annotation is considerably more informative for predicting the consequence of rare non-coding variants than for common variants. In summary, through transcriptome analyses within a large family we are able to identify the contribution of rare non-coding variants to expression phenotypes and further demonstrate the predictive potential of diverse non-coding genome annotation for interpretation of the impact of rare non-coding variants. RNA-Sequencing of CEPH/UTAH family 1463