Project description:Tissue resident macrophages are key players in inflammatory processes and their activation and functionality is crucial in health and disease. Diseases associated with alterations in homeostasis or dysregulation of the innate immune system are numerous and include allergic reactions, autoimmune diseases as well as cancer. Hence, these cells are of high interest in drug development. Currently, the main sources of macrophages used in drug development are still primary cells isolated from blood or tissue, or immortalized cell lines (e.g. THP-1). Here, we describe an improved method for large-scale production of tissue resident macrophages from induced pluripotent stem cells (iPSC) in unprecedented yields. For this, iPSC-derived macrophages are thoroughly characterized to confirm their cell identity and thus their suitability for screening purposes. We demonstrate that this method to generate macrophages from iPSC overcomes the limitations of using primary cells, i.e. donor variability and limited availability of large cell numbers. Notably, the cells recapitulate key functional characteristics, including cytokine release, phagocytosis and migration. Genetic modifications can be introduced at the macrophage progenitor stage, so this methodology will facilitate the generation of reporters and gain- and loss-of-function mutants in an isogenetic background, essential assets for target validation.
Project description:We showed novel synthetic microRNA (miRNA) switch system, which can purify large quantities of iPSC-CMs using magnetic-activated cell sorting (MACS). We used miR-208a, which is specifically expressed in cardiomyocytes, as a specific miRNA of CMs, and CD4 as a selection marker for MACS. We synthesized a miRNA switch encoding CD4 tagged with complementary sequences against miR-208a (miR-208a CD4 switch). We transfected this switch into differentiated cells, and easily got efficiently purified CMs in a large scale with MACS. In addition, we demonstrated that purified cells were shown to be engrafted as CMs in mouse hearts.
Project description:Development of a Large-Scale Chemogenomics Database to Improve Drug Candidate Selection and to Understand Mechanisms of Chemical Toxicity and Action These data support the publication titled "Development of a Large-Scale Chemogenomics Database to Improve Drug Candidate Selection and to Understand Mechanisms of Chemical Toxicity and Action" Copyright (c) 2005 by Iconix Pharmaceuticals, Inc. Guidelines for commercial use: http://www.iconixbiosciences.com/guidelineCommUse.pdf Keywords: other
Project description:Development of a Large-Scale Chemogenomics Database to Improve Drug Candidate Selection and to Understand Mechanisms of Chemical Toxicity and Action These data support the publication titled "Development of a Large-Scale Chemogenomics Database to Improve Drug Candidate Selection and to Understand Mechanisms of Chemical Toxicity and Action" Copyright (c) 2005 by Iconix Pharmaceuticals, Inc. Guidelines for commercial use: http://www.iconixbiosciences.com/guidelineCommUse.pdf Keywords: other
Project description:Here we utilized large-scale systematic probing and screening of ~2000 sequence and structural variants based on two long, perfect RNA hairpins to explore the structure and sequence context determining editability.