Noninvasive ultrasound stimulation of the spleen to treat inflammatory arthritis - single cell RNA sequencing of splenic leukocytes
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE125316 | GEO | 2019/01/19
REPOSITORIES: GEO
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Project description:Noninvasive ultrasound stimulation of the spleen to treat inflammatory arthritis - single cell RNA sequencing of splenic leukocytes
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Project description:Targeted noninvasive control of the nervous system and end-organs may enable safer and more effective treatment of multiple diseases compared to invasive devices or systemic medications. One target is the cholinergic anti-inflammatory pathway that consists of the vagus nerve to spleen circuit, which has been stimulated with implantable devices to improve autoimmune conditions such as rheumatoid arthritis. Here we report that daily noninvasive ultrasound (US) stimulation targeting the spleen significantly reduces disease severity in a mouse model of inflammatory arthritis. Improvements are observed only with specific parameters, in which US can provide both protective and therapeutic effects. Single cell RNA sequencing of splenocytes and experiments in genetically-immunodeficient mice reveal the importance of both T and B cell populations in the anti-inflammatory pathway. These findings demonstrate the potential for US stimulation of the spleen to treat inflammatory diseases.
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Project description:Echo-contrast agents enhance the echogenicity of ultrasound and have been clinically used for diagonosis in current medical fields. Here, the combined effects of Sonazoid, an echo-contrast agent, and ultrasound on the gene expression in human lymphoma U937 cells were investigated using an Affymetrix GeneChip system. The cells were treated with Sonazoid (0.05%; Sonazoid only), ultrasound (0.3 W/cm2 for 1 min; ultrasound only) and the combination of Sonazoid and ultrasound (0.05% Sonazoid plus ultrasound 0.3 W/cm2 for 1 min; Sonazoid + Ultrasound) and followed by incubation for 3 h at 37°C. The percentage of DNA fragmentation 6 h after treatment was 5.8 ± 1.0 (mean ± SD, n = 3), 6.0 ± 0.4, 13.5 ± 1.0, and 18.3 ± 2.3 in cells treated with control, Sonazoid only, ultrasound only and Sonazoid + Ultrasound, respectively. Of approximately 47,000 probe sets analyzed, probe sets that were differentially expressed by a factor 2.0 or greater were 40, 184 and 144 in cells treated with Sonazoid only, ultrasound only and Sonazoid + Ultrasound, respectively. Experiment Overall Design: U937 cells, a human lymphoma cell line, were treated with Sonazoid (0.05%), ultrasound (0.3 W/cm2 for 1 min) and the combination of Sonazoid and ultrasound (0.05% Sonazoid plus ultrasound 0.3 W/cm2 for 1 min) and followed by incubation for 3 h at 37°C. Non-treated cells were served as control. Total RNA samples were prepared from the cells. Gene expression was analyzed by an Affymetrix GeneChip® system with a Human Genome U133-plus 2.0 array for analysis of over 47,000 transcripts. Sample preparation for array hybridization was carried out as described in the manufacturerâ??s instructions.
2009-05-27 | E-GEOD-16118 | biostudies-arrayexpress
Project description:Echo-contrast agents enhance the echogenicity of ultrasound and have been clinically used for diagonosis in current medical fields. Here, the combined effects of Sonazoid, an echo-contrast agent, and ultrasound on the gene expression in human lymphoma U937 cells were investigated using an Affymetrix GeneChip system. The cells were treated with Sonazoid (0.05%; Sonazoid only), ultrasound (0.3 W/cm2 for 1 min; ultrasound only) and the combination of Sonazoid and ultrasound (0.05% Sonazoid plus ultrasound 0.3 W/cm2 for 1 min; Sonazoid + Ultrasound) and followed by incubation for 3 h at 37°C. The percentage of DNA fragmentation 6 h after treatment was 5.8 ± 1.0 (mean ± SD, n = 3), 6.0 ± 0.4, 13.5 ± 1.0, and 18.3 ± 2.3 in cells treated with control, Sonazoid only, ultrasound only and Sonazoid + Ultrasound, respectively. Of approximately 47,000 probe sets analyzed, probe sets that were differentially expressed by a factor 2.0 or greater were 40, 184 and 144 in cells treated with Sonazoid only, ultrasound only and Sonazoid + Ultrasound, respectively.
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Project description:The Ultrasound Study of Tamoxifen
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Project description:Torpor is an energy-conserving state in which animals dramatically decrease their metabolic rate and body temperature to survive harsh environmental conditions. Here, we report the noninvasive, precise, and safe induction of a torpor-like hypothermic and hypometabolic state in rodents by remote transcranial ultrasound stimulation at the hypothalamus preoptic area (POA). We achieve a long-lasting (> 24 hours) torpor-like state in mice via closed-loop feedback control of ultrasound stimulation with automated detection of body temperature. Ultrasound-induced hypothermia and hypometabolism (UIH) is triggered by activation of POA neurons, involves the dorsomedial hypothalamus as a downstream brain region and subsequent inhibition of thermogenic brown adipose tissue. Single-nucleus RNA-sequencing of POA neurons reveals TRPM2 as an ultrasound-sensitive ion channel, the knockdown of which suppresses UIH. We also demonstrate that UIH is feasible in a non-torpid animal, the rat. Our findings establish UIH as a promising technology for the noninvasive and safe induction of a torpor-like state. To investigate the mechanism of ultrasound-induced neuronal activation, we applied ultrasound stimulation in hypothalamic preoptic area region and performed single-nuclei RNA sequencing in the ultrasound stimulated neurons (US+) and neurons without ultrasound stimulation (US-). In our sn-RNAseq analysis, we examined the association between the expression of neuronal activation markers (or IEGs) and ion channels, as well as neuron types.
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Project description:Moderate selenium deficiency may lead to an impaired capacity to cope with health challenges. Functional effects of suboptimal selenium intake are not fully known, and biomarkers for an insufficient selenium supply are inadequate. We therefore fed mice diets of moderately deficient or adequate selenium intake for 6 weeks. Changes in global gene expression were monitored by microarray analysis in splenic leukocytes. Genes for four selenoproteins, Sepw1, Gpx1, Selh and Sep15, were the most significantly down-regulated in moderate selenium deficiency, and this was confirmed by quantitative polymerase chain reaction (qPCR). Classification of significantly affected genes revealed that processes related to inflammation, heme biosynthesis, DNA replication and transcription, cell cycle and transport were affected by selenium restriction. Down-regulation by moderate selenium deficiency of specific genes involved in inflammation and heme biosynthesis was confirmed by qPCR. Myeloperoxidase and lysozyme activities were decreased in selenium-restricted leukocytes, providing evidence for functional consequences. Genes for 31 nuclear factor (NF)-κB targets were down-regulated in moderate selenium deficiency, indicating an impaired NF-κB signaling. Together, the observed changes point to a disturbance in inflammatory response. The selenoproteins found here to be sensitive to selenium intake in murine leukocytes might also be useful as biomarkers for a moderate selenium deficiency in humans.
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