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TREM2 sustains macrophage-hepatocyte metabolic coordination in NAFLD and sepsis

ABSTRACT: TREM2 sustains macrophage-hepatocyte metabolic coordination in NAFLD and sepsis

PROVIDER: PRJNA672169 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12888200_1.fastq.gz	Fastqsanger.gz
	SRR12888200_2.fastq.gz	Fastqsanger.gz
	SRR12888300.fastq.gz	Fastqsanger.gz
	SRR12888201_1.fastq.gz	Fastqsanger.gz
	SRR12888201_2.fastq.gz	Fastqsanger.gz

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TREM2 sustains macrophage-hepatocyte metabolic coordination in NAFLD and sepsis [Mouse_Kupffer_cell_RNA_seq]

Project description:TREM2 sustains macrophage-hepatocyte metabolic coordination in NAFLD and sepsis [Mouse_Kupffer_cell_RNA_seq]

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TREM2 sustains macrophage-hepatocyte metabolic coordination in NAFLD and sepsis [Mouse_Kupffer_cell_small_RNA_seq]

Project description:TREM2 sustains macrophage-hepatocyte metabolic coordination in NAFLD and sepsis [Mouse_Kupffer_cell_small_RNA_seq]

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TREM2 sustains macrophage-hepatocyte metabolic coordination in NAFLD and sepsis [Mouse_liver_RNA_seq]

Project description:TREM2 sustains macrophage-hepatocyte metabolic coordination in NAFLD and sepsis [Mouse_liver_RNA_seq]

| PRJNA672232 | ENA

TREM2 sustains macrophage-hepatocyte metabolic coordination in NAFLD and sepsis [Human_liver_RNA_seq]

Project description:TREM2 sustains macrophage-hepatocyte metabolic coordination in NAFLD and sepsis [Human_liver_RNA_seq]

| PRJNA671636 | ENA

TREM2 sustains macrophage-hepatocyte metabolic coordination in NAFLD and sepsis [Mouse_Kupffer_cell_small_RNA_seq]

Project description:The goals of this study are to assess the NAFLD-induced changes in expression of hepatic Kupffer cells (KCs) miRNAs, we conducted deep sequencing of small RNAs from KCs isolated from 8-week HFD-fed WT and Trem2-/- mice. Over 1000 miRNAs were identified in the hepatic macrophages. A set of miRNAs were upregulated in Trem2-/- versus WT hepatic macrophages, amongh which miR-106b was the most abundant miRNA in KCs.

2021-02-17 | GSE160020 | GEO

TREM2 sustains macrophage-hepatocyte metabolic coordination in NAFLD and sepsis [Mouse_liver_RNA_seq]

Project description:The goals of this study are to corroborate whether Trem2 has a protective role against metabolic dysfunction and progression in a mouse model of NAFLD. We further performed an unbiased transcriptome analysis from the livers of 8-week HFD-fed WT versus Trem2–/– mice. In this screen, a cluster of 104 transcripts were up-regulated and 57 were down-regulated in response to Trem2 deficiency. Among these differentially expressed genes (adjusted P < 0.05), gene sets that contribute to fatty acid metabolic dysfunction, collagen fibril organization and cytokine secretion were significantly enriched in Trem2–/– livers, whereas long-chain/unsaturated fatty acid metabolic process and monocarboxylic acid metabolic process were overrepresented among WT livers.

2021-02-17 | GSE160021 | GEO

TREM2 sustains macrophage-hepatocyte metabolic coordination in NAFLD and sepsis [Mouse_Kupffer_cell_RNA_seq]

Project description:The goals of this study are to explore the potential mechanism underlying fatty acid oxidation defects in high fat diet (HFD)-fed Trem2-/- livers, we performed RNA-seq and profiled Kupffer cells (KCs) transcriptomes isolated from 8-week HFD-fed Trem2-/- mice and WT littermates. Gene ontology (GO) analysis revealed that antigen processing and presentation, mitochondrial oxidative phosphorylation and ATP synthesis were impaired in Trem2-/- KCs. However, gene links to chemotaxis (Ccr2, Cx3cr1, Spp1), cytokine secretion (Cd36, Acsl1, Mmp19) were upregulated in Trem2-/- KCs. Interestingly, positively regulated genes in RNA polymerase II-mediated pri-miRNA transcription (Bmp2, Klf4) and exsomes (Exos) secretion (Cd63, Cd9) were enriched in Trem2-/- KCs.

2021-02-17 | GSE160017 | GEO

TREM2 sustains macrophage-hepatocyte metabolic coordination in NAFLD and sepsis [Human_liver_RNA_seq]

Project description:The goals of this study are to investigate whether the defects of energy metabolism and/or mitochondria occurs in Nonalcoholic fatty liver disease (NAFLD), we performed liver transcriptome analysis from livers of donors who underwent organ donation after cardiac death (DCD; 6 non-NAFLD donors, 5 NAFLD donors). In this screen, a cluster of 462 transcripts were up-regulated and 447 transcripts were down-regulated in response to NAFLD. Among these differentially expressed genes , gene sets that contribute to endoplasmic reticulum stress, intrinsic apoptosis and cytokine production were enriched in NAFLD livers, whereas lipid metabolic process were suppressed in NAFLD livers, accompanied with deficient expression of the mitochondrial matrix enzyme.

2021-02-17 | GSE160016 | GEO

TREM2 sustains macrophage-hepatocyte metabolic coordination in NAFLD and sepsis

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-02-17 | GSE160022 | GEO

TREM2 sustains macrophage-hepatocyte metabolic coordination in nonalcoholic fatty liver disease and sepsis.

Project description:Sepsis is a leading cause of death in critical illness, and its pathophysiology varies depending on preexisting medical conditions. Here we identified nonalcoholic fatty liver disease (NAFLD) as an independent risk factor for sepsis in a large clinical cohort and showed a link between mortality in NAFLD-associated sepsis and hepatic mitochondrial and energetic metabolism dysfunction. Using in vivo and in vitro models of liver lipid overload, we discovered a metabolic coordination between hepatocyte mitochondria and liver macrophages that express triggering receptor expressed on myeloid cells-2 (TREM2). Trem2-deficient macrophages released exosomes that impaired hepatocytic mitochondrial structure and energy supply because of their high content of miR-106b-5p, which blocks Mitofusin 2 (Mfn2). In a mouse model of NAFLD-associated sepsis, TREM2 deficiency accelerated the initial progression of NAFLD and subsequent susceptibility to sepsis. Conversely, overexpression of TREM2 in liver macrophages improved hepatic energy supply and sepsis outcome. This study demonstrates that NAFLD is a risk factor for sepsis, providing a basis for precision treatment, and identifies hepatocyte-macrophage metabolic coordination and TREM2 as potential targets for future clinical trials.

| S-EPMC7880419 | biostudies-literature

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