Granulocyte-monocyte progenitors (GMPs) and monocyte-dendritic cell progenitors (MDPs) produce monocytes during homeostasis and in response to increased demand during infection. Both progenitor populations are thought to derive from common myeloid progenitors (CMPs), and a hierarchical relationship (CMP-GMP-MDP-monocyte) is presumed to underlie monocyte differentiation. Here, however, we demonstrate that mouse MDPs arose from CMPs independently of GMPs, and that GMPs and MDPs produced monocytes via similar, but distinct, monocyte-committed progenitors. GMPs and MDPs yielded classical (Ly6Chi) monocytes with gene expression signatures that were defined by their origins and impacted their function. GMPs produced a subset of “neutrophil-like” monocytes, whereas MDPs gave rise to a subset of monocytes that yielded monocyte-derived dendritic cells. GMPs and MDPs were also independently mobilized to produce specific combinations of myeloid cell types following the injection of microbial components. Thus, the balance of GMP and MDP differentiation shapes the myeloid cell repertoire during homeostasis and following infection. Overall design: RNA-seq of myeloid progenitors and Ly6Chi monocytes from mouse bone marrow. 4 progenitor fractions (GMPs, MDPs, GPs and a mixed fraction of MPs + cMoPs) were isolated from the pooled bone marrow of 20 mice. GMPs and MDPs were also cultured in vitro and the monocyte-committed progenitors and Ly6Chi monocytes they produced were also harvested. RNA was extracted from the 4 ex vivo progenitor fractions, and the 4 populations derived in vitro (GMP-derived monocyte progenitors = MP; MDP-derived monocyte progenitors = cMoP; GMP-derived Ly6Chi monocytes = G-mono; MDP-derived Ly6Chi monocytes = M-mono). The whole process was repeated using 20 additional mice to obtain a replicate set of samples.
Granulocyte-Monocyte Progenitors and Monocyte-Dendritic Cell Progenitors Independently Produce Functionally Distinct Monocytes.
Specimen part, Cell line, Subject
View SamplesWe used Affymetrix microarrays to investigate gene expression changes in the liver of lean female Zucker rats exposed to a normal diet supplemented with a rosemary extract rich in the diterpenic compound, carnosic acid (CA).
A rosemary extract enriched in carnosic acid improves circulating adipocytokines and modulates key metabolic sensors in lean Zucker rats: Critical and contrasting differences in the obese genotype.
Sex, Specimen part, Treatment, Time
View SamplesAIMS/HYPOTHESIS: Manoeuvres aimed at increasing beta cell mass have been proposed as regenerative medicine strategies for diabetes treatment. Raf-1 kinase inhibitor protein 1 (RKIP1) is a common regulatory node of the mitogen-activated protein kinase (MAPK) and nuclear factor B (NF-B) pathways and therefore may be involved in regulation of beta cell homeostasis. The aim of this study was to investigate the involvement of RKIP1 in the control of beta cell mass and function.
The role of Raf-1 kinase inhibitor protein in the regulation of pancreatic beta cell proliferation in mice.
Age, Specimen part
View SamplesWe used Affymetrix microarrays to investigate gene expression changes in PBMNCs isolated from female and male pigs to determine significant modulatory effects that may have been induced by the intake of resveratrol during 9 months in high-fat fed animals .
Effects of long-term consumption of low doses of resveratrol on diet-induced mild hypercholesterolemia in pigs: a transcriptomic approach to disease prevention.
Sex, Specimen part, Time
View SamplesWe used Affymetrix microarrays to investigate gene expression changes in PBMCs isolated from male patients ongoing secondary prevention of CVD to determine significant modulatory effects that may have been induced by the intake of an initial dose of 8 mg of resveratrol-enriched grape extract for 6 months and then, 16 mg for a further 6 months.
One-year supplementation with a grape extract containing resveratrol modulates inflammatory-related microRNAs and cytokines expression in peripheral blood mononuclear cells of type 2 diabetes and hypertensive patients with coronary artery disease.
Sex, Specimen part, Time
View SamplesExpansions of a hexanucleotide repeat (GGGGCC) in the noncoding region of the C9orf72 gene are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Decreased expression of C9orf72 is seen in expansion carriers, suggesting loss of function may play a role in disease. We find that two independent mouse lines lacking the C9orf72 ortholog (3110043O21Rik) in all tissues developed normally and aged without motor neuron disease. Instead, C9orf72 null mice developed progressive splenomegaly and lymphadenopathy with accumulation of engorged macrophage-like cells. C9orf72 expression was highest in myeloid cells, and loss of C9orf72 led to lysosomal accumulation and altered immune responses in macrophages and microglia, with age-related neuroinflammation similar to C9orf72 ALS but not sporadic ALS patient tissue. Thus, C9orf72 is required for normal function of myeloid cells, and altered microglial function may contribute to neurodegeneration in C9orf72 expansion carriers. Overall design: To compare the RNA Seq profiles from the lumbar region of spinal cords from mice lacking one copy or both copies of the C9orf72 ortholog (3110043O21Rik) compared to wild type control with two copies at 3 months (n=3) and 17 months (n=4).
C9orf72 is required for proper macrophage and microglial function in mice.
Specimen part, Cell line, Subject
View SamplesThe spatial organization of chromosomes influences many nuclear processes including gene expression. The cohesin complex shapes the 3D genome by looping together CTCF sites along chromosomes. We show here that chromatin loop size can be increased, and that the duration with which cohesin embraces DNA determines the degree to which loops are enlarged. Cohesin's DNA release factor WAPL restricts the degree of this loop extension and also prevents looping between incorrectly oriented CTCF sites. We reveal that the SCC2/SCC4 complex promotes the extension of chromatin loops and the formation of topologically associated domains (TADs). Our data support the model that cohesin structures chromosomes through the processive enlargement of loops and that TADs reflect polyclonal collections of loops in the making. Finally, we find that whereas cohesin promotes chromosomal looping, it rather limits nuclear compartmentalization. We conclude that the balanced activity of SCC2/SCC4 and WAPL enables cohesin to correctly structure chromosomes. Overall design: RNAseq was performed in control, ?WAPL 3.3, ?WAPL 1.14, ?SCC4 and ?WAPL/?SCC4 cells in triplicate.
The Cohesin Release Factor WAPL Restricts Chromatin Loop Extension.
Cell line, Subject
View SamplesTreatment of prostate cancer by hormone suppression leads to the appearance of aggressive variants with variable or no dependence on the androgen receptor. Here we show that the developmental transcription factor, ONECUT2, is a master regulator of the AR network that is highly active in castration-resistant prostate cancer (CRPC).
ONECUT2 is a targetable master regulator of lethal prostate cancer that suppresses the androgen axis.
Cell line, Treatment
View SamplesTo evaluate the specificity for inhibition of expression of OC2 target genes we generated microarray data of 22Rv1 cells treated for 4, 6 and 16 hours with the small molecule inhibitor.
ONECUT2 is a targetable master regulator of lethal prostate cancer that suppresses the androgen axis.
Cell line, Treatment, Time
View Samples