Project description:To further reveal the major cell types of developing pIVC embryos and underlying epigenetic dynamics, the optimized single-cell based multi-omics sequencing method scChaRM-seq was performed (Yan et al., 2021b). 1,862 single cells Bisulfite-seq datasets were further analyzed. We then performed multi-omics profiling analysis using data obtained from9 pIVC embryos at 8 sequential developmental stages.
Project description:To uncover the role of opioid induced dysbiosis in disrupting intestinal homeostasis, we conducted a multi-omics analysis with gut microbial, metabolite and intestinal transcriptomics data
Project description:To uncover the role of opioid induced dysbiosis in disrupting intestinal homeostasis, we conducted a multi-omics analysis with gut microbial, metabolite and intestinal transcriptomics data
Project description:In mammals, circadian rhythms are entrained to the light cycle and drive daily oscillations in levels of NAD+ a co-substrate of the class III histone deacetylase SIRT1 that associates with clock transcription factors. While NAD+ also participates in redox reactions, the extent to which NAD(H) couples nutrient state with circadian transcriptional cycles remains unknown. Here we show that nocturnal animals subjected to time-restricted feeding of a calorie-restricted diet (TRF-CR) only during nighttime display reduced body temperature and elevated hepatic NADH during daytime. Genetic uncoupling of nutrient state from NADH redox state through transduction of the water-forming NADH oxidase from Lactobacillus brevis (LbNOX) increases daytime body temperature and blood and liver acyl-carnitines. LbNOX expression in TRF-CR mice induces oxidative gene networks controlled by BMAL1 and PPARa and suppresses amino acid catabolic pathways. Enzymatic analyses reveal that NADH inhibits SIRT1 in vitro, corresponding with reduced deacetylation of SIRT1 substrates during TRF-CR in vivo. Remarkably, Sirt1 liver nullizygous animals subjected to TRF-CR display persistent hypothermia even when NADH is oxidized by LbNOX. Our findings reveal that the hepatic NADH cycle links nutrient state to whole-body energetics through the rhythmic regulation of SIRT1.
Project description:To further reveal the major cell types of developing pIVC embryos and underlying epigenetic dynamics, the optimized single-cell based multi-omics sequencing method scChaRM-seq was performed (Yan et al., 2021b). After stringent filtration, 3,682 single cells RNA-seq datasets were further analyzed We then performed multi-omics profiling analysis using data obtained from9 pIVC embryos at 8 sequential developmental stages.
Project description:The gut microbiome has been implicated in multiple human chronic gastrointestinal (GI) disorders. Determining its mechanistic role in disease pathogenesis has been difficult due to the apparent disconnect between animal and human studies and a lack of an integrated multi-omics view in the context of disease-specific physiological changes. We integrated longitudinal multi-omics data from the gut microbiome, metabolome, host epigenome and transcriptome in the context of irritable bowel syndrome (IBS) host physiology. We identified IBS subtype-specific and symptom-related variation in microbial composition and function. A subset of identified changes in microbial metabolites correspond to host physiological mechanisms that are relevant to IBS. By integrating multiple data layers, we identified purine metabolism as a novel host-microbial metabolic pathway in IBS with translational potential. Our study highlights the importance of longitudinal sampling and integrating complementary multi-omics data to identify functional mechanisms that can serve as therapeutic targets in a comprehensive treatment strategy for chronic GI diseases.
Project description:In these experiments, we aimed to investigate the role of cardiomyocyte-specific deletion of the G-quadruplex resolvase Dhx36 in heart development and cardiomyocyte differentiation. To achieve this, we conducted multi-omics analysis using single-nuclei RNA sequencing (RNA-seq) and ATAC sequencing (ATAC-seq) on hearts from postnatal day 7 (PD7) wild-type (WT) and Dhx36 conditional knockout (cKO) mice. Our findings reveal that Dhx36 plays a critical role in the development of the cardiac conduction system (CCS) and in the differentiation of both CCS and working cardiomyocytes
Project description:In these experiments, we aimed to investigate the role of cardiomyocyte-specific deletion of the G-quadruplex resolvase Dhx36 in heart development and cardiomyocyte differentiation. To achieve this, we conducted multi-omics analysis using single-nuclei RNA sequencing (RNA-seq) and ATAC sequencing (ATAC-seq) on hearts from postnatal day 7 (PD7) wild-type (WT) and Dhx36 conditional knockout (cKO) mice. Our findings reveal that Dhx36 plays a critical role in the development of the cardiac conduction system (CCS) and in the differentiation of both CCS and working cardiomyocytes