ELABELA (ELA) is a peptide hormone required for heart development that signals via the Apelin Receptor (APLNR, APJ). ELA is also abundantly secreted by human embryonic stem cells (hESCs), which do not express APLNR. Here we show that ELA signals in a paracrine fashion in hESCs to maintain self-renewal. ELA inhibition by CRISPR/Cas9-mediated deletion, shRNA or neutralizing antibodies causes reduced hESC growth, cell death and loss of pluripotency. Global phosphoproteomic and transcriptomic analyses of ELA-pulsed hESCs show that it activates PI3K/AKT/mTORC1 signaling required for cell survival. ELA promotes hESC cell cycle progression and protein translation, and blocks stress-induced apoptosis. INSULIN and ELA have partially overlapping functions in hESC medium, but only ELA can potentiate the TGF pathway to prime hESCs towards the endoderm lineage. We propose that ELA, acting through an alternate cell-surface receptor, is an endogenous secreted growth factor in human embryos and hESCs that promotes growth and pluripotency.
ELABELA Is an Endogenous Growth Factor that Sustains hESC Self-Renewal via the PI3K/AKT Pathway.
Specimen part, Treatment
View SamplesPaeoniflorin (PF) isolated from paeony root (Paeoniae radix) has been used as an herbal medicine in East Asis for its anti-allergic, anti-inflammatory, and immunoregulatory effects. PF is known to be a chemical heat shock protein (HSP) inducer. The effects on the gene expression in human lymphoma U937 cells treated with PF were investigated using by an Affymetrix GeneChip system. PF treatment induced Hsp70 expression in U937 cells in a dose- and time-dependent manner as shown in Western blot analysis. When the cells were treated with PF (160 g/ml; 30 min), 41 up-regulated and 23 down-regulated genes were identified.
Identification of genes responsive to paeoniflorin, a heat shock protein-inducing compound, in human leukemia U937 cells.
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View SamplesWe established the differentiation method of a limb bud organoid from mouse embryonic stem cells (mESCs) using SFEBq. mESCs-derived limb bud organoid selectively differentiate into forelimb or hindlimb by adjusting the retinoic acids activity. To evaluate a correlation of gene expression between limb bud organoid and embryonic tissues (limb bud, branchial arch, cardiac, and tail bud), we performed comparative transcriptome analysis using RNA-seq. Overall design: RNA-seq profiling of mouse embryonic limb bud, branchial arch, cardiac, and tail bud and mESCs-derived forelimb and hindlimb bud mesenchyme (Hnad2::GFP positive), in triplicate, using illumina Hi-seq.
Self-organized formation of developing appendages from murine pluripotent stem cells.
Specimen part, Cell line, Subject
View SamplesIn order to identify genes that are activated in differentiating WT ESCs, but are missing in Tal-1-/- and Runx1-/- ESCs, and which might be involved in the generation of definitive hematopoietic progenitors and their specification thereafter, we performed microarray analyses on purified Flk-1+ cells, differentiated from these ESCs for 4, 5, and 6 days in vitro.
Ectopic Runx1 expression rescues Tal-1-deficiency in the generation of primitive and definitive hematopoiesis.
Specimen part, Cell line, Time
View SamplesWe analyzed liver gene expression from male and female ARE-Del mice, which have prolonged and chronic expression of IFN gamma through deletion of the IFN gamma 3’ UTR AU-rich element. Overall design: Compare liver gene expression from male and female ARE-Del compared to control littermates (n=3)
Chronic expression of interferon-gamma leads to murine autoimmune cholangitis with a female predominance.
Sex, Age, Specimen part, Cell line, Subject
View SamplesDiet-induced obesity is reported to induce a phenotypic switch in adipose tissue macrophages from an antiinflammatory M2 state to a proinflammatory M1 state. Telmisartan, an angiotensin II type 1 receptor antagonist and a peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist, reportedly has beneficial effects on insulin sensitivity. We studied the effects of telmisartan on the adipose tissue macrophage phenotype in high fat-fed mice. Telmisartan was administered for 5 weeks to high fat-fed C57BL/6 mice. Insulin sensitivity, macrophage infiltration, and the gene expressions of M1 and M2 markers in epididymal fat tissues were examined. Insulin- or a glucose-tolerance test showed that telmisartan treatment improved insulin resistance, decreasing the body weight gain, visceral fat weight and adipocyte size without affecting the amount of food intake. Telmisartan treatment reduced the number of CD11c-positive cells and crown-like structures. Telmisartan reduced the mRNA expressions of M1 macrophage markers, such as TNF-alpha and IL-6, and increased the expression of M2 markers, such as IL-10 and Mgl2. The reduction of M1 macrophage markers, as well as the increased gene expression of M2 markers especially IL-10, is a possible mechanism for the improvement of insulin sensitivity by telmisartan.
Telmisartan improves insulin resistance and modulates adipose tissue macrophage polarization in high-fat-fed mice.
Sex, Specimen part, Treatment
View SamplesThe onset of the liver inflamentation in the Sox17+/- embryos.
Sox17 haploinsufficiency results in perinatal biliary atresia and hepatitis in C57BL/6 background mice.
Specimen part
View SamplesTreatment of DBA/2J mice with a combination of L-methionine and valproic acid significantly attenuated progressive hearing loss. We examined gene expression in the whole cochlea of the mice. This study was aimed to detect genes of which change in expression levels were associated with attenuation of progressive hearing loss in the mice.
Attenuation of progressive hearing loss in DBA/2J mice by reagents that affect epigenetic modifications is associated with up-regulation of the zinc importer Zip4.
Sex, Age, Specimen part
View SamplesObjectives: Sex hormone receptors are reported to be present in human dental pulp (HDP) cells. The purpose of this study was to examine the biological significance of estrogen and androgen receptors (ER and AR, respectively) in HDP cells. Design: We isolated HDP cells expressing ER- and AR-mRNAs and investigated the expression status of the receptors and the response to sex hormones in the cells. Results: HDP cells expressing ER- and/or AR-mRNAs had the ability to form alizarin red S-positive nodules in which calcium and phosphorus were deposited in vitro and to differentiate into odontoblasts-like cells and dentin-like tissue in vivo. Individual clones isolated from HDP cells exhibited a different expression pattern of mRNA for ER and AR. Some clones expressed ER- and/or ER-mRNAs and the others coexpressed ER- and AR-mRNAs. Using the Ingenuity software, we found that 17-estradiol (E2) and dihydrotestosterone (DHT) could act directly on HDP cells through ER- or androgen signaling-mediated mechanisms. E2 or DHT stimulated the mRNA expression for genes related to odontogenesis of dentin-containing teeth and odontoblast differentiation, suggesting that ER and AR in HDP cells may be involved in dentinogenesis. Conclusions: Our findings provide new insights into the biological significance of sex hormone receptors in HDP cells.
Expression status of mRNA for sex hormone receptors in human dental pulp cells and the response to sex hormones in the cells.
Sex, Specimen part, Treatment
View SamplesMacaca fascicularis (long-tailed, cynomolgus, or crab-eating macaque) is a highly advantageous model in which to study human cochlea with regard to both evolutionary proximity and physiological similarity of the auditory system. To better understand the properties of primate cochlear function, we analyzed the genes predominantly expressed in M. fascicularis cochlea.
Gene expression dataset for whole cochlea of Macaca fascicularis.
Sex, Age, Specimen part
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