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GSE32034
Mus musculus
1 Downloadable Sample
Description
PPAR is known for its anti-inflammatory actions in macrophages. However, which macrophage populations express PPAR in vivo and how it regulates tissue homeostasis in the steady state and during inflammation is not completely understood. We show that lung and spleen macrophages constitutively expressed PPAR, while other macrophage populations did not. Recruitment of monocytes to sites of inflammation was associated with induction of PPAR as they differentiated to macrophages. Its absence in these macrophages led to failed resolution of inflammation, characterized by persistent, low-level recruitment of leukocytes. Conversely, PPAR agonists supported an earlier cessation in leukocyte recruitment during resolution of acute inflammation and likewise suppressed monocyte recruitment to chronically inflamed atherosclerotic vessels. In the steady state, PPAR deficiency in macrophages had no obvious impact in the spleen but profoundly altered cellular lipid homeostasis in lung macrophages. Reminiscent of pulmonary alveolar proteinosis, LysM-Cre x PPARflox/flox mice displayed mild leukocytic inflammation in the steady-state lung and succumbed faster to mortality upon infection with S. pneumoniae. Surprisingly, this mortality was not due to overly exuberant inflammation, but instead to impaired bacterial clearance. Thus, in addition to its anti-inflammatory role in promoting resolution of inflammation, PPAR sustains functionality in lung macrophages and thereby has a pivotal role in supporting pulmonary host defense.
Publication Title
Systemic analysis of PPARĪ³ in mouse macrophage populations reveals marked diversity in expression with critical roles in resolution of inflammation and airway immunity.
Sample Metadata Fields
Sex, Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
Description
Human and mouse blood each contain two monocyte subsets. Here, we investigated the extent of their similarity using a microarray approach. Approximately 300 genes in human and 550 genes in mouse were differentially expressed between subsets. More than 130 of these gene expression differences were conserved between mouse and human monocyte subsets. We confirmed numerous differences at the cell surface protein level. Despite overall conservation, some molecules were conversely expressed between the two species subsets, including CD36, CD9, and TREM-1. Furthermore, other differences existed, including a prominent PPAR signature in mouse monocytes absent in human. Overall, human and mouse monocyte subsets are far more broadly conserved than currently recognized. Thus, studies in mice may indeed yield relevant information regarding the biology of human monocyte subsets. However, differences between the species deserve consideration in models of human disease studied in the mouse.
Publication Title
Comparison of gene expression profiles between human and mouse monocyte subsets.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 16 Downloadable Samples
Illumina NovaSeq 6000
Description
Study objectives: Chronic obstructive pulmonary disease and obstructive sleep apnea overlap syndrome is associated with excess mortality, and outcomes are related to the degree of hypoxemia. People at high altitude are susceptible to periodic breathing, and hypoxia at altitude is associated with cardio-metabolic dysfunction. Hypoxemia in these scenarios may be described as superimposed sustained plus intermittent hypoxia, or overlap hypoxia (OH), the effects of which have not been investigated. We aimed to characterize the cardio-metabolic consequences of OH in mice. Methods: C57BL/6J mice were subjected to either sustained hypoxia (SH, FiO2=0.10), intermittent hypoxia (IH, FiO2=0.21 for 12 hours, and FiO2 oscillating between 0.21 and 0.06, 60 times/hour, for 12 hours), OH (FiO2=0.13 for 12 hours, and FiO2 oscillating between 0.13 and 0.06, 60 times/hour, for 12 hours), or room air (RA), n=8/group. Blood pressure and intraperitoneal glucose tolerance test were measured serially, and right ventricular systolic pressure (RVSP) was assessed. Results: Systolic blood pressure transiently increased in IH and OH relative to SH and RA. RVSP did not increase in IH, but increased in SH and OH by 52% (p<0.001) and 20% (p=0.001). Glucose disposal worsened in IH and improved in SH, with no change in OH. Serum LDL and VLDL increased in OH and SH, but not in IH. Hepatic oxidative stress increased in all hypoxic groups, with the highest increase in OH. Conclusions: Overlap hypoxia may represent a unique and deleterious cardio-metabolic stimulus, causing systemic and pulmonary hypertension, and without protective metabolic effects characteristic of sustained hypoxia. Overall design: Whole liver mRNA profiles of C57BL/6J mice exposed to RA, SH, IH, or OH.
Publication Title
Combined intermittent and sustained hypoxia is a novel and deleterious cardio-metabolic phenotype.
Sample Metadata Fields
Age, Specimen part, Genotype, Treatment, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
Description
The object of this study was to identify genes transcriptionally upregulated and downregulated in response to Tcof1 haploin-sufficiency during mouse embryogensis
Publication Title
Prevention of the neurocristopathy Treacher Collins syndrome through inhibition of p53 function.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 86 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Dynamic regulatory network controlling TH17 cell differentiation.
Sample Metadata Fields
Specimen part, Treatment
View Samples