Dataset Information

Integrative Transcriptome Analyses of Metabolic Responses in Mice Define Pivotal LncRNA Metabolic Regulators.

ABSTRACT: To systemically identify long noncoding RNAs (lncRNAs) regulating energy metabolism, we performed transcriptome analyses to simultaneously profile mRNAs and lncRNAs in key metabolic organs in mice under pathophysiologically representative metabolic conditions. Of 4,759 regulated lncRNAs, function-oriented filters yield 359 tissue-specifically regulated and metabolically sensitive lncRNAs that are predicted by lncRNA-mRNA correlation analyses to function in diverse aspects of energy metabolism. Specific regulations of liver metabolically sensitive lncRNAs (lncLMS) by nutrients, metabolic hormones, and key transcription factors were further defined in primary hepatocytes. Combining genome-wide screens, bioinformatics function predictions, and cell-based analyses, we developed an integrative roadmap to identify lncRNA metabolic regulators. An lncLMS was experimentally confirmed in mice to suppress lipogenesis by forming a negative feedback loop in the SREBP1c pathway. Taken together, this study supports that a class of lncRNAs function as important metabolic regulators and establishes a framework for systemically investigating the role of lncRNAs in physiological homeostasis.

SUBMITTER: Yang L

PROVIDER: S-EPMC5181118 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Integrative Transcriptome Analyses of Metabolic Responses in Mice Define Pivotal LncRNA Metabolic Regulators.

Yang Ling L Li Ping P Yang Wenjing W Ruan Xiangbo X Kiesewetter Kurtis K Zhu Jun J Cao Haiming H

Cell metabolism 20160922 4

To systemically identify long noncoding RNAs (lncRNAs) regulating energy metabolism, we performed transcriptome analyses to simultaneously profile mRNAs and lncRNAs in key metabolic organs in mice under pathophysiologically representative metabolic conditions. Of 4,759 regulated lncRNAs, function-oriented filters yield 359 tissue-specifically regulated and metabolically sensitive lncRNAs that are predicted by lncRNA-mRNA correlation analyses to function in diverse aspects of energy metabolism. S ...[more]

PMID: 27667668

Similar Datasets

Project description:It remains unclear why some patients infected with SARS-CoV-2 readily resolve infection while others develop severe disease. To address this question, we employed a novel assay to interrogate immune-metabolic programs of T cells and myeloid cells in severe and recovered COVID-19 patients. Using this approach, we identified a unique population of T cells expressing high H3K27me3 and the mitochondrial membrane protein voltage-dependent anion channel (VDAC), which were expanded in acutely ill COVID-19 patients and distinct from T cells found in patients infected with hepatitis c or influenza and in recovered COVID-19. Increased VDAC was associated with gene programs linked to mitochondrial dysfunction and apoptosis. High-resolution fluorescence and electron microscopy imaging of the cells revealed dysmorphic mitochondria and release of cytochrome c into the cytoplasm, indicative of apoptosis activation. The percentage of these cells was markedly increased in elderly patients and correlated with lymphopenia. Importantly, T cell apoptosis could be inhibited in vitro by targeting the oligomerization of VDAC or blocking caspase activity. In addition to these T cell findings, we also observed a robust population of Hexokinase II+ polymorphonuclear-myeloid derived suppressor cells (PMN-MDSC), exclusively found in the acutely ill COVID-19 patients and not the other viral diseases. Finally, we revealed a unique population of monocytic MDSC (M-MDSC) expressing high levels of carnitine palmitoyltransferase 1a (CPT1a) and VDAC. The metabolic phenotype of these cells was not only highly specific to COVID-19 patients but the presence of these cells was able to distinguish severe from mild disease. Overall, the identification of these novel metabolic phenotypes not only provides insight into the dysfunctional immune response in acutely ill COVID-19 patients but also provide a means to predict and track disease severity as well as an opportunity to design and evaluate novel metabolic therapeutic regimens.

Dataset Information

Integrative Transcriptome Analyses of Metabolic Responses in Mice Define Pivotal LncRNA Metabolic Regulators.

Publications

Integrative Transcriptome Analyses of Metabolic Responses in Mice Define Pivotal LncRNA Metabolic Regulators.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets