Hematopoiesis occurs in a microenviroenment in which stromal cells are prominent. Stromal cells have been shown to maintain stem cell behaviour of hematopoietic stem cells. We derived several different stromal cell lines from midgestation embryos which will, or will not maintain hemetopoietic stem cells in cultures.
Efficient hematopoietic differentiation of human embryonic stem cells on stromal cells derived from hematopoietic niches.
No sample metadata fields
View SamplesThe underlying mechanisms which are responsible and govern early haematopoietic differentiation during development are poorly understood. Gene expression comparison between pluripotent human embryonic stem cells and earliest haematopoietic progenitors may reveal novel transcripts and pathways and provide crucial insight into early haematopoietic lineage specification and development.
Large-scale transcriptional profiling and functional assays reveal important roles for Rho-GTPase signalling and SCL during haematopoietic differentiation of human embryonic stem cells.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Screening and validation of lncRNAs and circRNAs as miRNA sponges.
Cell line
View SamplesIntensive research in past two decades has uncovered the presence and importance of noncoding RNAs (ncRNAs), which includes microRNAs (miRs) and long ncRNAs (lncRNAs). These two classes of ncRNAs interact to a certain extent, as some lncRNAs bind to miRs to sequester them. Such lncRNAs are collectively called 'competing endogenous RNAs' or 'miRNA sponges'. In this study, we screened for lncRNAs that may act as miRNA sponges using the publicly available data sets and databases. To uncover the roles of miRNA sponges, loss-of-function experiments were conducted, which revealed the biological roles as miRNA sponges. LINC00324 is important for the cell survival by binding to miR-615-5p leading to the de-repression of its target BTG2 LOC400043 controls several biological functions via sequestering miR-28-3p and miR-96-5p, thereby changing the expressions of transcriptional regulators. Finally, we also screened for circular RNAs (circRNAs) that may function as miRNA sponges. The results were negative at least for the selected circRNAs in this study. In conclusion, miRNA sponges can be identified by applying a series of bioinformatics techniques and validated with biological experiments.
Screening and validation of lncRNAs and circRNAs as miRNA sponges.
Cell line
View SamplesIn order to provide functional data of kidney-specific long intergenic non-coding RNAs (lincRNA), loss-of-function study was conducted.
Logic programming to infer complex RNA expression patterns from RNA-seq data.
Cell line
View SamplesMicroRNAs are endogenously expressed small non-coding RNAs that regulate gene expression on the posttranscriptional level. The miR-17-92 cluster (encoding miR-17, -18a, -19a/b, -20a and miR-92a) is highly expressed in tumor cells and is up-regulated by ischemia. Whereas miR-92a was recently identified as negative regulator of angiogenesis, the specific functions of the other members of the cluster are less clear. Here we demonstrate that overexpression of miR-17, -18a, -19a and -20a significantly inhibited 3D spheroid sprouting in vitro, whereas inhibition of miR-17, -18a and -20a augmented endothelial cell (EC) sprout formation. Inhibition of miR-17 and miR-20a in vivo using antagomirs significantly increased the number of perfused vessels in matrigel plugs, whereas antagomirs, that specifically target miR-18a and miR-19a were less effective. However, systemic inhibition of miR-17/20 did not affect tumor angiogenesis. Further mechanistic studies showed that miR-17/20 targets several pro-angiogenic genes. Specifically, Janus kinase 1 (Jak1) was shown to be a direct target of miR-17. In summary, we show that miR-17/20 exhibit a cell intrinsic anti-angiogenic activity in ECs. Inhibition of miR-17/20 specifically augmented neovascularization of matrigel plugs, but did not affect tumor angiogenesis indicating a context-dependent regulation of angiogenesis by miR-17/20 in vivo.
Members of the microRNA-17-92 cluster exhibit a cell-intrinsic antiangiogenic function in endothelial cells.
Specimen part
View SamplesIn order to identify genes regulated by VE-cadherin expression, we compared a mouse VE-cadherin null cell line (VEC null) with the same line reconstituted with VE-cadherin wild type cDNA (VEC positive). The morphological and functional properties of these cell lines were described previously [Lampugnani,M.G. et al. Contact inhibition of VEGF-induced proliferation requires vascular endothelial cadherin, beta-catenin, and the phosphatase DEP-1/CD148. J. Cell Biol. 161, 793-804 (2003)]. By Affymetrix gene expression analysis we found several genes up-regulated by VE-cadherin, among which claudin-5 reached remarkably high levels. The up-regulation of these genes required not only VE-cadherin expression but also cell confluence suggesting that VE-cadherin clustering at junctions was needed.
Endothelial adherens junctions control tight junctions by VE-cadherin-mediated upregulation of claudin-5.
No sample metadata fields
View SamplesHuman umbilical vein endothelial cells (HUVECs) were incubated for 48 h after transfection of scrambled siRNA or siRNA targeting Jmjd6 .
Jumonji domain-containing protein 6 (Jmjd6) is required for angiogenic sprouting and regulates splicing of VEGF-receptor 1.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Human tissues contain CD141hi cross-presenting dendritic cells with functional homology to mouse CD103+ nonlymphoid dendritic cells.
Sex, Specimen part, Disease, Disease stage
View SamplesDendritic cells (DCs) are critical in mediating immunity to pathogens, vaccines, tumors and tolerance to self. Significant progress has been made in the study of DC subsets in murine models but the translation of these findings to human DC immunobiology has not been fully realized. Murine splenic CD8+ DC and CD103+ DC possess potent antigen cross-presenting capacity. Although recent evidence points to human blood CD141+ DCs as the functional equivalent of CD8+ DC, the precise identity of the human migratory cross-presenting DC has remained elusive. We performed phenotypic and functional analyses to interrogate the DC compartment of human non-lymphoid tissues and identified three distinct subsets: i) CD141high DCs, ii) CD1c DCs and iii) CD14+ DCs. Only CD141high DCs were capable of cross-presenting soluble antigen. Comparative transcriptome analysis of steady state monocyte and DC subsets between mouse and human confirmed conservation between species, aligning the following subsets together: i) human CD141high DCs with mouse CD8+ and CD103+ DCs, ii) human CD1c+ DCs with mouse CD4+ DCs and iii) human CD14+ DC with mouse monocyte subsets. The lack of positive association between human CD1c+ DCs and mouse non-lymphoid tissue CD11b+ DCs highlights heterogeneity and predicts the existence of a monocyte-like cell within the CD11b+ DCs.
Human tissues contain CD141hi cross-presenting dendritic cells with functional homology to mouse CD103+ nonlymphoid dendritic cells.
Specimen part, Disease, Disease stage
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