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Next Generation Sequencing Facilitates Quantitative Analysis of adipose tissue Treg and LN Treg Transcriptomes

ABSTRACT: Next Generation Sequencing Facilitates Quantitative Analysis of adipose tissue Treg and LN Treg Transcriptomes

PROVIDER: PRJNA513260 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8403111_1.fastq.gz	Fastqsanger.gz
	SRR8403111_2.fastq.gz	Fastqsanger.gz
	SRR8403112_1.fastq.gz	Fastqsanger.gz
	SRR8403112_2.fastq.gz	Fastqsanger.gz
	SRR8403113_1.fastq.gz	Fastqsanger.gz

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Next Generation Sequencing Facilitates Quantitative Analysis of adipose tissue Treg and LN Treg Transcriptomes

Project description:The goal of this study is to reveal unique features of adipose Tregs and to study mechanisms underlying how mediator Med23 regulate adipose Treg function in aged mice. Therefore, mRNA profiles of LN Tregs (from 4-month old Foxp3Cre mice) and adipose Tregs (from 4-month old Foxp3Cre, 4-month old obese Foxp3Cre, 10-month old Foxp3Cre and 10-month old Med23fl/fl;Foxp3Cre mice) were generated by deep sequencing, single experiment, using Illumina HiSeq2000. We compared transcriptome features between lymph node-derived Tregs and adipose Tregs from 4-month old lean or obese mice. Using unbiased comparative gene expression analyses, we found adipose Tregs display an up-signature of Insr (Insulin receptor) and Hif1a, while Pparg acts as a positive control. We next compared gene expression profiles of adipose Tregs from 10-month old Med23fl/fl;Foxp3Cre (MKO) and Foxp3Cre (WT) mice. adipose Med23-ΔTreg cells display impaired transcription of Pparg and Il1rl1 (ST2), and they simultaneously acquire the expression of Nt5e (CD73), while Entpd1 (CD39) expression was not dramatically altered. Our studies implicate protective roles of CD73hi adipose Tregs and offer new therapeutic strategies against age-associated metabolic syndrome.

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Single-cell ATAC-Sequencing of adipose Treg cells

Project description:Systematic characterizations of adipose Treg subsets and their in vivo roles remain uncommon. The goal of this study is to reveal the heterogeneity and chromatin landscape of adipose Treg cells. Using single-cell ATAC-seq to map adipose Treg cells, we identified different adipose subsets. Strikingly, our scATAC-seq analysis revealed a strong enrichment of key transcription factor motifs, which may play function in fate specification. By gain and loss of function studies, we further demonstrated adipose Treg subsets display disparate physiologic influences. Our findings have important implications for understanding phenotypic diversity of tissue Tregs in vivo.

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Project description:The goal of this study is to study mechanisms underlying how HIF-1α regulates adipose Treg function. Therefore, mRNA profiles of adipose Tregs (from 4-month old Foxp3Cre and Hif1afl/fl;Foxp3Cre mice) were generated by deep sequencing, single experiment, using Illumina HiSeq TEN. We compared gene expression profiles of adipose Tregs from Hif1afl/fl;Foxp3Cre and Foxp3Cre mice. Using unbiased comparative gene expression analyses, we found adipose HIF-1α-ΔTreg cells showed higher expression of Nt5e gene and simultaneously down-regulated canonical adipose Treg genes (including Pparg, Il1rl1, Klrg1, Areg). Therefore, these data suggested a dependency of HIF-1α on PPAR-γ expression in adipose Tregs.

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