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Microglia, the brain's resident macrophages, can be reconstituted by surrogate cells - a process termed 'microglia replacement'. To expand the microglia replacement toolkit, we here introduce estrogen-regulated (ER) homeobox B8 (Hoxb8) conditionally immortalized macrophages, a cell model for generation of immune cells from murine bone marrow, as a versatile model for microglia replacement. We find that ER-Hoxb8 macrophages are highly comparable to primary bone marrow-derived macrophages in vitro, and, when transplanted into a microglia-free brain, engraft the parenchyma and differentiate into microglia-like cells. Furthermore, ER-Hoxb8 progenitors are readily transducible by virus and easily stored as stable, genetically manipulated cell lines. As a demonstration of this system's power for studying the effects of disease mutations on microglia in vivo, we created stable, Adar1-mutated ER-Hoxb8 lines using CRISPR-Cas9 to study the intrinsic contribution of macrophages to Aicardi-Goutières syndrome (AGS), an inherited interferonopathy that primarily affects the brain and immune system. We find that Adar1 knockout elicited interferon secretion and impaired macrophage production in vitro, while preventing brain macrophage engraftment in vivo - phenotypes that can be rescued with concurrent mutation of Ifih1 (MDA5) in vitro, but not in vivo. Lastly, we extended these findings by generating ER-Hoxb8 progenitors from mice harboring a patient-specific Adar1 mutation (D1113H). We demonstrated the ability of microglia-specific D1113H mutation to drive interferon production in vivo, suggesting microglia drive AGS neuropathology. In sum, we introduce the ER-Hoxb8 approach to model microglia replacement and use it to clarify macrophage contributions to AGS.
Pubmed ID: 41589671
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Non-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Facilitates archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.
View all literature mentionsSoftware package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.
View all literature mentionsImaris provides range of capabilities for working with three dimensional images. Uses flexible editing and processing functions, such as interactive surface rendering and object slicing capabilities. And output to standard TIFF, Quicktime and AVI formats. Imaris accepts virtually all image formats that are used in confocal microscopy and many of those used in wide-field image acquisition.
View all literature mentionsSoftware for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.
View all literature mentionsSoftware package for the analysis of gene expression microarray data, especially the use of linear models for analyzing designed experiments and the assessment of differential expression.
View all literature mentionsNIH is the nations medical research agency - making important medical discoveries that improve health and save lives. The National Institutes of Health (NIH), a part of the U.S. Department of Health and Human Services, is the primary Federal agency for conducting and supporting medical research. Helping to lead the way toward important medical discoveries that improve peoples health and save lives, NIH scientists investigate ways to prevent disease as well as the causes, treatments, and even cures for common and rare diseases. NIH research impacts: * child and teen health, * men's health, * minority health, * seniors' health, * women's health, and * wellness and lifestyle issues. Composed of 27 Institutes and Centers, the NIH provides leadership and financial support to researchers in every state and throughout the world.
View all literature mentionsCloud platform to be directly integrated in to the industry?s leading sequencing platforms, with no cumbersome and time consuming data transfer steps.
View all literature mentionsNIAID research strives to understand, treat, and ultimately prevent the myriad infectious, immunologic, and allergic diseases that threaten millions of human lives. Major areas of investigation: * Acquired Immunodeficiency Syndrome (AIDS) * Asthma and Allergic Diseases * Biodefense * Emerging and Re-emerging Infectious Diseases * Enteric Diseases * Fundamental Immunology * Genetics and Transplantation * Immune-Mediated Diseases * Influenza * Pathogen Genomics * Sexually Transmitted Infections (STIs) * Vaccine Development * Drug Research and Development * Antimicrobial Resistance * Minority and Women''s Health
View all literature mentionsBioconductor software package for Empirical analysis of Digital Gene Expression data in R. Used for differential expression analysis of RNA-seq and digital gene expression data with biological replication.
View all literature mentionsNIGMS supports basic biomedical research that is not targeted to specific diseases. NIGMS funds studies on genes, proteins, and cells, as well as on fundamental processes like communication within and between cells, how our bodies use energy, and how we respond to medicines. The results of this research increase our understanding of life and lay the foundation for advances in disease diagnosis, treatment, and prevention. NIGMS also supports research training programs that produce the next generation of biomedical scientists, and it has special programs to encourage underrepresented minorities to pursue biomedical research careers. The National Institute of General Medical Sciences (NIGMS) primarily supports research that lays the foundation for advances in disease diagnosis, treatment, and prevention. The Institute's research training programs help provide the next generation of scientists. Each year, NIGMS-supported scientists make many advances in understanding fundamental life processes. In the course of answering basic research questions, these investigators increase our knowledge about the mechanisms and pathways involved in certain diseases. Institute grantees also develop important new tools and techniques, some of which have medical applications. In recognition of the significance of their work, a number of NIGMS grantees have received the Nobel Prize and other high scientific honors. At any given time, NIGMS supports approximately 4,700 research grants—approximately 11 percent of the grants funded by NIH as a whole. NIGMS also supports approximately 26 percent of the trainees who receive assistance from NIH. NIGMS also supports approximately 25% of the trainees who receive assistance from NIH. The Institute places great emphasis on supporting investigator-initiated research grants. It funds a limited number of research center grants in selected fields, including structural genomics, trauma and burn research, and systems biology. In addition, NIGMS supports several important scientific resources, including the NIGMS Human Genetic Cell Repository and the Protein Data Bank.
View all literature mentionsAn independent federal agency created by Congress to promote the progress of science; to advance the national health, prosperity, and welfare; to secure the national defense They are the funding source for approximately 20 percent of all federally supported basic research conducted by America''s colleges and universities. In many fields such as mathematics, computer science and the social sciences, NSF is the major source of federal backing. NSF leadership has two major components: a director who oversees NSF staff and management responsible for program creation and administration, merit review, planning, budget and day-to-day operations; and a 24-member National Science Board (NSB) of eminent individuals that meets six times a year to establish the overall policies of the foundation.The director and all Board members serve six year terms. Each of them, as well as the NSF deputy director, is appointed by the President of the United States and confirmed by the U.S. Senate. At present, NSF has a total workforce of about 2,100 at its Arlington, Va., headquarters, including approximately 1,400 career employees, 200 scientists from research institutions on temporary duty, 450 contract workers and the staff of the NSB office and the Office of the Inspector General. NSF is the only federal agency whose mission includes support for all fields of fundamental science and engineering, except for medical sciences. They are tasked with keeping the United States at the leading edge of discovery in areas from astronomy to geology to zoology. So, in addition to funding research in the traditional academic areas, the agency also supports high-risk, high pay-off ideas, novel collaborations and numerous projects that may seem like science fiction today, but which the public will take for granted tomorrow. And in every case, they ensure that research is fully integrated with education so that today''s revolutionary work will also be training tomorrow''s top scientists and engineers NSF''s task of identifying and funding work at the frontiers of science and engineering is not a top-down process.
View all literature mentionsNational institute whose mission is to reduce the burden of neurological disease - a burden borne by every age group, by every segment of society, by people all over the world. To accomplish this goal the NINDS supports and conducts basic, translational, and clinical research on the normal and diseased nervous system. The Institute also fosters the training of investigators in the basic and clinical neurosciences, and seeks better understanding, diagnosis, treatment, and prevention of neurological disorders. NINDS: * Conducts, fosters, coordinates, and guides research on the causes, prevention, diagnosis, and treatment of neurological disorders and stroke, and supports basic research in related scientific areas. * Provides grants-in-aid to public and private institutions and individuals in fields related to its areas of interest, including research project, program project, and research center grants. * Operates a program of contracts for the funding of research and research support efforts in selected areas of institute need. * Provides individual and institutional fellowships to increase scientific expertise in neurological fields. * Conducts a diversified program of intramural and collaborative research in its own laboratories, branches, and clinics. * Collects and disseminates research information related to neurological disorders.
View all literature mentionsOpen source software package for statistical programming language R to create plots based on grammar of graphics. Used for data visualization to break up graphs into semantic components such as scales and layers.
View all literature mentionsData aggregate that compiles results from bioinformatics analyses across multiple samples into a single report. It is written in Python.
View all literature mentionsWeb tool for graphical illustrations for biological systems by BioRender. Used for articles and presentations. Collection of pre made icons and templates from life science fields for scientific illustrations. Customized icons possible on request.
View all literature mentionsWeb tool to estimates spectrum and frequency of small insertions and deletions generated in pool of cells by genome editing tools such as CRISPR/Cas9, TALENs and ZFNs. Used for quantification of small indels in DNA of targeted cell pool. Provides rapid and reliable assessment of genome editing experiments of target locus.
View all literature mentionsProvides digital infrastructure, data analytics and decision support tools to help in diagnosis, treatment and monitoring of patients.
View all literature mentionsMus musculus with name FVB/NJ from IMSR.
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