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Noninvasive ultrasound stimulation of the spleen to treat inflammatory arthritis - single cell RNA sequencing of splenic leukocytes

ABSTRACT: Noninvasive ultrasound stimulation of the spleen to treat inflammatory arthritis - single cell RNA sequencing of splenic leukocytes

PROVIDER: PRJNA515851 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8457100.fastq.gz	Fastqsanger.gz
	SRR8457110.fastq.gz	Fastqsanger.gz
	SRR8457120.fastq.gz	Fastqsanger.gz
	SRR8457101.fastq.gz	Fastqsanger.gz
	SRR8457111.fastq.gz	Fastqsanger.gz

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Noninvasive ultrasound stimulation of the spleen to treat inflammatory arthritis - single cell RNA sequencing of splenic leukocytes

Project description:Purpose: The goal of this study was to characterize splenic leukocytes in arthritic and non-arthritic mice with and without ultrasound treatment

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Noninvasive ultrasound stimulation of the spleen to treat inflammatory arthritis.

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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Induction of a torpor-like hypothermic and hypometabolic state in rodents by ultrasound

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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Transcription profiling of human leukemia U937 cells treated with the combination of Sonazoid and ultrasound

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 37Â°C. The percentage of DNA fragmentation 6 h after treatment was 5.8 Â± 1.0 (mean Â± SD, n = 3), 6.0 Â± 0.4, 13.5 Â± 1.0, and 18.3 Â± 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 37Â°C. Non-treated cells were served as control. Total RNA samples were prepared from the cells. Gene expression was analyzed by an Affymetrix GeneChipÂ® 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.

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