Project description:Utilizing a chronic colitis model in Apoe-deficient mice, we identify the crucial role of neutrophils in the development of atherosclerosis. We demonstrate that neutrophils are the first cells to respond in both the circulation and the aorta to the repetitive stimulus of chronic intestinal inflammation and acquire inflammatory, pathogenic phenotype. Single cell RNA-Seq and single cell ATAC-Seq analysis of sorted GMP popu;ation revealed that circulating bone marrow neutrophils from repeated DSS-exposed mice acquire the pathogenic phenotype in the bone marrow which can accelerate vascular inflammation in turn.
Project description:Utilizing a chronic colitis model in Apoe-deficient mice, we identify the crucial role of neutrophils in the development of atherosclerosis. We demonstrate that neutrophils are the first cells to respond in both the circulation and the aorta to the repetitive stimulus of chronic intestinal inflammation and acquire inflammatory, pathogenic phenotype. Single cell RNA-Seq and single cell ATAC-Seq analysis of sorted GMP popu;ation revealed that circulating bone marrow neutrophils from repeated DSS-exposed mice acquire the pathogenic phenotype in the bone marrow which can accelerate vascular inflammation in turn.
Project description:Deciphering cis-regulatory logic underlying cell type identity is a fundamental question in biology. Single-cell chromatin accessibility (scATAC-seq) data has enabled training of sequence-to-function deep learning models allowing decoding of enhancer logic and design of synthetic enhancers. Training such models requires large amounts of high-quality training data across species, organs, development, aging, and disease. To facilitate the cost-effective generation of large scATAC-seq atlases for model training, we developed a new version of the open-source microfluidic system HyDrop with increased sensitivity and scale: HyDrop v2. We generated HyDrop-v2 atlases for the mouse cortex and Drosophila embryo development and compared them to atlases generated on commercial platforms. HyDrop-v2 data integrates seamlessly with commercially available chromatin accessibility methods (10x Genomics). Differentially accessible regions and motif enrichment across cell types are equivalent between HyDrop-v2 and 10x atlases. Sequence-to-function models trained on either atlas are comparable as well in terms of enhancer predictions, sequence explainability, and transcription factor footprinting. By offering accessible data generation, enhancer models trained on HyDrop-v2 and mixed atlases can contribute to unraveling cell-type specific regulatory elements in health and disease.
Project description:Plasmodium-specific CD4+ T cells from mice infected with Plasmodium chabaudi chabaudi AS parasites were recovered at Days 0, 4, 7, and 32 to undergo processing and to generate scATAC-seq dataset. At Day 7, CXCR5+ and CXCR6+ cells were recovered separately. At Day 32, mice were administered with either saline or artesunate (intermittent artesunate therapy - IAT). scATAC-seq dataset was analysed to investigate epigenomic landscapes of CD4+ T cells from effector to memory states.
Project description:To study developmental trajectories in brain organoids, we conducted scRNA-seq and scATAC-seq in parallel on a dense timecourse of early development.
Project description:Cardiovascular disease accounts for one in every four deaths in the United States and is the single largest cause of mortality around the world. The most common cause of cardiovascular-related deaths are due to development of occlusive atherosclerotic plaques. A hallmark event in the development of atherosclerotic plaque is the accumulation of lipid-laden macrophages in the subendothelial layers of affected blood vessels. Macrophages are key players in all stages of atherogenesis, including plaque initiation, growth, rupture, as well as healing of ruptured plaques. In this context, macrophages are the principal innate immune cells that modulate atherogenesis by engaging in various processes such as inflammation, extracellular matrix degradation, phagocytosis, and efferocytosis. Here, we report that macrophage Kruppel-like factor 6 (KLF6) deficiency attenuates pro-inflammatory gene expression and experimentally induced atherosclerotic plaque development. Our in vivo studies show that myeloid-KLF6 deficiency on Apoe-null background significantly curtails high-fat/high-cholesterol diet-induced atherosclerotic lesion formation and macrophage abundance in atherosclerotic plaques. Integrated transcriptomics and Gene Set Enrichment Analysis show that KLF6 deficiency significantly attenuates a large number of TNF-induced gene targets, and TNF-induced IFN response, IFN response, and inflammatory response signaling in macrophages. At the molecular level, KLF6 promotes IRF1 signaling to enhance TNF-induced pro-inflammatory gene expression in macrophages. Collectively, our analyses show that KLF6 promotes pro-inflammatory gene expression in macrophages and boosts experimentally induced atherosclerotic plaque formation in vivo.