The cellular ontogeny of hematopoietic stem cells (HSCs) remains poorly understood because their isolation from and their identification in early developing small embryos are difficult. We attempted to dissect early developmental stages of HSCs using an in vitro mouse embryonic stem cell (ESC) differentiation system combined with inducible HOXB4 expression. Here we report the identification of pre-HSCs and an embryonic type of HSCs (embryonic HSCs) as intermediate cells between ESCs and HSCs. Both pre-HSCs and embryonic HSCs were isolated by their c-Kit+CD41+CD45- phenotype. Pre-HSCs did not engraft in irradiated adult mice. After co-culture with OP9 stromal cells and conditional expression of HOXB4, pre-HSCs gave rise to embryonic HSCs capable of engraftment and long-term reconstitution in irradiated adult mice. Blast colony assays revealed that most hemangioblast activity was detected apart from the pre-HSC population, implying the early divergence of pre-HSCs from hemangioblasts. Gene expression profiling suggests that a particular set of transcripts closely associated with adult HSCs is involved in the transition of pre-HSC to embryonic HSCs.
Stepwise development of hematopoietic stem cells from embryonic stem cells.
Treatment
View SamplesAnalysis of mouse chondrocytes lacking the microRNA-140. MicroRNAs are genomically encoded small RNAs to regulate the gene expression. miR-140 shows high expression in cartilage. Results provide insight into the molecular mechanisms underlying miR-140 function in chondrocytes.
MicroRNA-140 plays dual roles in both cartilage development and homeostasis.
Specimen part
View SamplesWe previously found that mice with heterozygous knockout of the alpha-isoform of calcium/calmodulin-dependent protein kinase II (alpha-CaMKII HKO mice) show various dysregulated behaviors, including cyclic variations in locomotor activity (LA), suggesting that alpha-CaMKII HKO mice may serve as an animal model showing infradian oscillation of mood. We performed gene expression microarray analysis of dentate gyrus from alpha-CaMKII HKO mice. Mice were selected for the sampling such that their LA levels varied among the mice.
Circadian Gene Circuitry Predicts Hyperactive Behavior in a Mood Disorder Mouse Model.
Specimen part
View SamplesTWEAK/Fn14 signaling may regulate the expression of genes involved in epithelial repair and mucosal inflammation. Comparing the gene signatures in WT and TWEAK KO mice will inform the biology of TWEAK/Fn14 pathway in the GI tract.
Interleukin-13 damages intestinal mucosa via TWEAK and Fn14 in mice-a pathway associated with ulcerative colitis.
Specimen part, Treatment
View SamplesPolarization of macrophages to M1 or M2 cells is important for mounting responses against bacterial and helminth infection respectively. Jumonji domain containing 3 (JMJD3), a histone 3 K27 demethylase, has been implicated in the activation of macrophages. Here we show that JMJD3 is essential for M2 macrophage polarization to helminth infection and chitin, though JMJD3 is dispensable for M1 responses. Furthermore, Jmjd3 is critical for proper bone marrow macrophage differentiation in a demethylase activity-dependent manner. Jmjd3 deficiency affected trimethylation of H3K27 in only a limited numbers of genes. Among them, we identified Irf4 as the target transcription factor critical for controlling M2 macrophage polarization. Collectively, these results show that JMJD3-mediated H3K27 demethylation is critical for regulating M2 macrophage development leading to anti-helminth host responses.
The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection.
Specimen part, Treatment
View SamplesKRAP (Ki-ras-induced actin-interacting protein) is a cytoskeleton-associated protein and a ubiquitous protein among tissues, originally identified as a cancer-related molecule. KRAP-deficient (KRAP-/-) mice show enhanced metabolic rate, decreased adiposity, improved glucose tolerance, hypoinsulinemia and hypoleptinemia. KRAP-/- mice are also protected against high-fat diet-induced obesity and insulin resistance despite of hyperphagia.
Altered energy homeostasis and resistance to diet-induced obesity in KRAP-deficient mice.
No sample metadata fields
View SamplesKRAP (Ki-ras-induced actin-interacting protein) is a cytoskeleton-associated protein and a ubiquitous protein among tissues, originally identified as a cancer-related molecule. KRAP-deficient (KRAP-/-) mice show enhanced metabolic rate, decreased adiposity, improved glucose tolerance, hypoinsulinemia and hypoleptinemia. KRAP-/- mice are also protected against high-fat diet-induced obesity and insulin resistance despite of hyperphagia.
Altered energy homeostasis and resistance to diet-induced obesity in KRAP-deficient mice.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Forced expression of the histone demethylase Fbxl10 maintains self-renewing hematopoietic stem cells.
Specimen part
View SamplesMouse CD34(-)KSL hematopoietic stem cells and CD34(+)KSL multipotent progenitors were purified by cell sorting from bone marrow of 8-week-old C57BL/6 mice, and their gene expression was analyzed.
Forced expression of the histone demethylase Fbxl10 maintains self-renewing hematopoietic stem cells.
Specimen part
View SamplesThis array set was used to identify the genes that are highly expressed in the mouse suprachiasmatic nucleus (SCN). Because pharmacological inhibition of Gai/o activity with pertussis toxin hampers intercellular synchronization and causes dampened rhythms of the entire SCN, we hypothesized that member(s) of the Regulator of G protein Signaling (RGS) family might contribute to synchronized cellular oscillations in the SCN. To test this hypothesis, we surveyed all known mouse Rgs genes for their expression by using GeneChip and selected the genes that are highly expressed in the SCN for further analysis.
Circadian regulation of intracellular G-protein signalling mediates intercellular synchrony and rhythmicity in the suprachiasmatic nucleus.
Sex, Age, Specimen part, Disease, Treatment, Time
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