We performed a global analysis of both miRNAs and mRNAs expression across sixteen human cell lines and extracted negatively correlated pairs of miRNA and mRNA which indicate miRNA-target relationship. The many of known-target of miR-124a showed negative correlation, suggesting our analysis were valid. We further extracted physically relevant miRNA-target gene pairs, applying computational target prediction algorism with inverse correlations of miRNA and mRNA expression. Furthermore, Gene Ontology-based annotation and functional enrichment analysis of the extracted miRNA-target gene pairs indicated putative functions of miRNAs.
Global correlation analysis for micro-RNA and mRNA expression profiles in human cell lines.
No sample metadata fields
View SamplesMicroRNAs are small non-coding RNA species, some of which are playing important roles in cell differentiation. However, the level of participations of microRNAs in epithelial cell differentiation is largely unknown. Here, we found that expression levels of four microRNAs (miR-210, miR-338-3p, miR-33a and miR-451) were significantly increased in differentiated stage of T84 cells, compared with undifferentiated stage. Additionally, we demonstrate that miR-338-3p and miR-451 contribute to the formation of epithelial basolateral polarity by facilitating translocalization of beta1 integrin to the basolateral membrane. However, candidate target mRNAs of miR-338-3p and miR-451 and the mechanism behind observed phenomena is uncertain. Then, we performed comprehensive gene expression analysis to identify candidate target mRNAs and understand their mechanisms.
MicroRNA-338-3p and microRNA-451 contribute to the formation of basolateral polarity in epithelial cells.
Cell line, Treatment, Time
View SamplesPeripheral circadian clocks regulate many aspects of physiology. In this study we deleted the core circadian clock component Bmal1 specifically in mouse adipocytes in order to study the role of the adipocyte clock in energy homeostasis and body weight. We used microarrays to indentify changes in gene expression in the adipose tissue of mice lacking a functional adipocyte circadian clock and identified a small number of up- and down- regulated genes.
Obesity in mice with adipocyte-specific deletion of clock component Arntl.
Specimen part
View SamplesIn previous studies, human dental pulp stem cells (hDPSCs) were mainly isolated from adults. In this manuscript, we tried characterization of hDPSCs isolated from an earlier developmental stage to evaluate potential usage of these cells for tissue regenerative therapy. hDPSCs isolated at the crown-completed stage showed a higher proliferation rate than those isolated at the later stage. When the cells from either group were cultured in medium promoting differentiation towards cells of the osteo/odontoblastic lineage, both became alkaline phosphatase positive, produced calcified matrix, and were also capable of forming dentin-like matrix on scaffolds in vivo. However, during long-term passage, these cells underwent a change in morphology and lost their differentiation ability. The results of a DNA array experiment showed that the expression of a number of genes, such as WNT16, was markedly changed with increasing number of passages, which might have caused the loss of their characteristics as hDPSCs.
Characterization of dental pulp stem cells of human tooth germs.
No sample metadata fields
View SamplesNeutrophils provide immune protection against pathogens but also may promote tissue injury in inflammatory diseases. Although neutrophils are generally considered as a relatively homogeneous population, evidence for heterogeneity is emerging. Under steady-state conditions, neutrophil heterogeneity may arise from ageing and the replenishment by newly released neutrophils from the bone marrow.
Neutrophil ageing is regulated by the microbiome.
Specimen part, Treatment
View SamplesThe spectrum of genetic mutations differs among cancers in different organs, implying a cellular context-dependent effect of the genetic aberrations. However, the extent to which the cellular context affects the consequences of oncogenic mutations remains to be fully elucidated. We reprogrammed colon tumor cells in an Apc Min/+ mouse model, in which the loss of the Apc gene plays a critical role in tumor development, and established reprogrammed tumor cells (RTCs) that exhibit pluripotent stem cell (PSC)-like signatures of gene expression. We show that the majority of the genes in the RTCs that were affected by the Apc mutations did not overlap with the genes that were affected in the intestine or those that were affected by the accumulation of beta-catenin in PSCs. The RTCs lacked pluripotency but exhibited the increased expression of Cdx2 and a differentiation propensity that was biased toward the trophectoderm cell lineage. The genetic rescue of the mutated Apc allele conferred pluripotency on the RTCs and enabled their differentiation into various cell types in vivo. The re-disruption of Apc in the RTC-derived differentiated cells resulted in neoplastic growth that was exclusive to the intestine, yet the majority of intestinal lesions remained pre-tumoral microadenomas. These results highlight the significant influence of the cellular context on gene regulation, cellular plasticity, and cellular behavior in response to the loss of the Apc function. Our results also imply that transition from microadenomas to macroscopic tumors is reprogrammable, which underscores the importance of epigenetic regulation on colon tumor promotion.
Cellular context-dependent consequences of Apc mutations on gene regulation and cellular behavior.
Specimen part
View SamplesCell cycle quiescence is a critical feature contributing to haematopoietic stem cell (HSC) maintenance. Although various candidate stromal cells have been identified as potential HSC niches, the spatial localization of quiescent HSC in the bone marrow (BM) remains unclear. Here, using a novel approach that combines whole-mount confocal immunofluorescence imaging technique and computational modelling to analyse significant tridimensional associations among vascular structures, stromal cells and HSCs, we show that quiescent HSCs associate specifically with small arterioles that are preferentially found in endosteal BM. These arterioles are ensheathed exclusively by rare Nestin-GFP-peri/NG2+ pericytes, distinct from sinusoid-associated Nestin-GFP-retic/LepR+ cells. The present RNA-seq study sought to obtain a comprehensive understanding of the differences between the two distinct HSC cellular niches. Overall design: mRNA profiles of sorted Nestin-GFP-peri and -GFP-retic bone marrow stromal cells were generated from pooled mice in triplicate by Illumina HiSeq 2000 sequencing.
Arteriolar niches maintain haematopoietic stem cell quiescence.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
EWS/ATF1 expression induces sarcomas from neural crest-derived cells in mice.
Specimen part
View SamplesWhereas the cellular basis of the hematopoietic stem cell (HSC) niche in the bone marrow has been characterized, the nature of the fetal liver (FL) niche is not yet elucidated. We show that Nestin+NG2+ pericytes associate with portal vessels, forming a niche promoting HSC expansion. Nestin+NG2+ cells and HSCs scale during development with the fractal branching patterns of portal vessels, tributaries of the umbilical vein. After closure of the umbilical inlet at birth, portal vessels undergo a transition from Neuropilin-1+Ephrin-B2+ artery to EphB4+ vein phenotype, associated with a loss of peri-portal Nestin+NG2+ cells and emigration of HSCs away from portal vessels. These data support a model in which HSCs are titrated against a peri-portal vascular niche with a fractal-like organization enabled by placental circulation. Overall design: Characterization of the transcriptome of fetal liver and adult bone marrow niche using RNA-seq
Fetal liver hematopoietic stem cell niches associate with portal vessels.
Specimen part, Cell line, Subject
View SamplesClear cell sarcoma (CCS) is an aggressive soft tissue malignant tumor characterized by a unique t(12; 22) translocation, leading to the expression of a chimeric EWS/ATF1 fusion gene. However, little is known about the mechanisms underlying how EWS/ATF1 is involved in the development of CCSs. In addition, the cells of origin for CCSs remain to be determined. We generated EWS/ATF1-inducible mice, and examined the effects of EWS/ATF1 expression in adult cells. We show that the forced expression of EWS/ATF1 results in the development of EWS/ATF1-dependent sarcomas in mice. The histology of EWS/ATF1-induced sarcomas resembles that of CCSs and EWS/ATF1-induced tumor cells express CCS-markers, such as S100, Sox10, and Mitf. A lineage tracing experiment revealed that such sarcomas are derived from neural crest-lineage cells. Finally, we found that EWS/ATF1 directly induces Fos in an ERK-independent manner, and demonstrated that the increased Fos expression is important for the active cell proliferation in not only EWS/ATF1-induced sarcomas, but also in human CCSs. Our results indicate that FOS, as well as EWS/ATF1 itself, could be a promising therapeutic target for the treatment of EWS/ATF1-related sarcomas.
EWS/ATF1 expression induces sarcomas from neural crest-derived cells in mice.
Specimen part
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