A5070900693- Immune cells in cancer
- Neuroinflammation and Neurodegeneration Mechanisms
- Immune Response and Inflammation
- Cancer-related molecular mechanisms research
- Genetic and phenotypic traits in livestock
- Alzheimer's disease research and treatments
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Peroxisome Proliferator-Activated Receptors
- Cytokine Signaling Pathways and Interactions
- Vector-borne infectious diseases
- Viral gastroenteritis research and epidemiology
- Neurological Disease Mechanisms and Treatments
- CRISPR and Genetic Engineering
- Veterinary medicine and infectious diseases
- Animal Virus Infections Studies
- Animal Genetics and Reproduction
- Animal Disease Management and Epidemiology
- Veterinary Equine Medical Research
- Virus-based gene therapy research
- Vector-Borne Animal Diseases
- Biochemical and Structural Characterization
- Livestock Farming and Management
- Migration, Racism, and Human Rights
- Insect symbiosis and bacterial influences
University of Edinburgh
2016-2025
Roslin Institute
2016-2024
UK Dementia Research Institute
2018-2024
Université Libre de Bruxelles
2018
Génétique Animale et Biologie Intégrative
2010-2016
<h3>Objective</h3> There is substantial inter-individual diversity in the susceptibility of alcoholics to liver injury. Alterations intestinal microbiota (IM) have been reported alcoholic disease (ALD), but extent which they are merely a consequence or cause unknown. We aimed demonstrate that specific dysbiosis contributes development hepatitis (AH). <h3>Design</h3> humanised germ-free and conventional mice using human IM transplant from patients with without AH. The consequences on...
Abstract The proliferation, differentiation and survival of mononuclear phagocytes depend on signals from the receptor for macrophage colony-stimulating factor, CSF1R. mammalian Csf1r locus contains a highly conserved super-enhancer, fms -intronic regulatory element (FIRE). Here we show that genomic deletion FIRE in mice selectively impacts CSF1R expression tissue development specific tissues. Deletion ablates murine embryonic stem cells. ΔFIRE/ΔFIRE lack macrophages embryo, brain microglia...
Rapid innovation in sequencing technologies and improvement assembly algorithms have enabled the creation of highly contiguous mammalian genomes. Here we report a chromosome-level water buffalo (Bubalus bubalis) genome using single-molecule chromatin conformation capture data. PacBio Sequel reads, with mean length 11.5 kb, helped to resolve repetitive elements generate sequence contiguity. All five B. bubalis sub-metacentric chromosomes were correctly scaffolded centromeres spanned. Although...
Sheep are a key source of meat, milk and fibre for the global livestock sector, an important biomedical model. Global analysis gene expression across multiple tissues has aided genome annotation supported functional mammalian genes. We present large-scale RNA-Seq dataset representing all major organ systems from adult sheep several juvenile, neonatal prenatal developmental time points. The Ovis aries reference (Oar v3.1) includes 27,504 genes (20,921 protein coding), which 25,350 (19,921...
We have produced Csf1r-deficient rats by homologous recombination in embryonic stem cells. Consistent with the role of Csf1r macrophage differentiation, there was a loss peripheral blood monocytes, microglia brain, epidermal Langerhans cells, splenic marginal zone macrophages, bone-associated macrophages and osteoclasts, peritoneal macrophages. Macrophages red pulp, liver, lung, gut were less affected. The pleiotropic impacts on development multiple organ systems distinct from those reported...
The F4/80 antigen, encoded by the Adgre1 locus, has been widely-used as a monocyte-macrophage marker in mice, but its value macrophage other species is unclear, and even questioned. ADGRE1 seven transmembrane G protein-coupled receptor with an extracellular domain containing repeated Epidermal Growth Factor (EGF)-like calcium binding domains. Using new monoclonal antibody, we demonstrated that myeloid differentiation pigs, absent from progenitors bone marrow, highly-expressed mature...
Abstract To differentiate between the contribution of mammary epithelial cells (MEC) and infiltrating immune to gene expression profiles tissue during early stage mastitis, we investigated in goats vivo transcriptional response MEC an experimental intra infection (IMI) with Staphylococcus aureus , using a non-invasive RNA sampling method from milk fat globules (MFG). Microarrays were used record patterns first 24 hours post-infection (hpi). This approach was combined laser capture...
Macrophage colony-stimulating factor (CSF1) is an essential growth and differentiation for cells of the macrophage lineage. To explore role CSF1 in steady-state control monocyte production tissue repair, we previously developed a bioactive protein with longer half-life circulation by fusing pig Fc region IgG1a. CSF1-Fc administration to pigs expanded progenitor pools marrow selectively increased numbers their expression maturation marker CD163. There was rapid increase size liver, extensive...
Abstract Activated mouse macrophages metabolize arginine via NO synthase (NOS2) to produce as an antimicrobial effector. Published gene expression datasets provide little support for the activation of this pathway in human macrophages. Generation requires coordinated regulation multiple genes. We have generated RNA-sequencing data from bone marrow–derived representative rodent (rat), monogastric (pig and horse), ruminant (sheep, goat, cattle, water buffalo) species, analyzed genes involved...
The domestic water buffalo (Bubalus bubalis) makes a major contribution to the global agricultural economy in form of milk, meat, hides and draught power. population is predominantly found Asia, per head more people depend upon than on any other livestock species. Despite its importance, there are comparatively fewer genomic transcriptomic resources available for We have generated large-scale gene expression atlas covering multiple tissue cell types from all organ systems collected three...
Microglial endolysosomal (dys)function is strongly implicated in neurodegenerative disease. Transcriptomic studies show that a microglial state characterised by set of genes involved function induced both mouse Alzheimer’s disease (AD) models and human AD brain, the emergence this emphasised females. Cst7 (encoding cystatin F) among most highly upregulated these microglia. However, despite such striking robust upregulation, not understood. Here, we crossed -/- mice with App NL-G-F to test...
Germ-line deletion of a conserved enhancer (the Fms intrinsic regulatory element, FIRE) in the mouse Csf1r locus causes congenital absence microglia. Homozygous FIRE on C57BL/6J background leads to perinatal lethality and hydrocephalus (HC) surviving pups. We developed congenic line with defined regions non-C57BL/6J genomic DNA, increased postnatal viability reduced incidence HC. Both HC were eliminated F2 mice following outcross CBA/J or BALBc/J backgrounds. To assess impacts microglial...
Cellular transformation is initiated by a driver mutation, resulting in the abnormal expression of an oncogene or loss tumor suppressor gene normal cell. This event leads to oncogenic stress (OS), describing disruption cellular homeostasis which activates response pathways and transcriptomic programs that can either promote development trigger intrinsic safeguards such as senescence apoptosis. While immunogenicity senescent cells well established, immunogenic potential at early OS stage...
Signaling via the colony-stimulating factor 1 receptor (CSF1R) controls survival, differentiation, and proliferation of macrophages. Mutations in CSF1 or CSF1R mice rats have pleiotropic effects on postnatal somatic growth. We tested possible application pig CSF1-Fc fusion protein as a therapy for low birth weight (LBW) at term, using model based maternal dexamethasone treatment rats. Neonatal did not alter growth increase blood monocyte count. Instead, there was substantial size liver both...
The response of the human acute myeloid leukemia cell line THP-1 to phorbol esters has been widely-studied test candidate therapies and as a model cycle arrest monocyte-macrophage differentiation. Here we have employed Cap Analysis Gene Expression (CAGE) analyse dense time course transcriptional regulation in cells treated with myristate acetate (PMA) over 96 hours. PMA treatment greatly reduced numbers entering S phase also blocked exiting G2/M. PMA-treated became adherent expression mature...
The laboratory rat is widely used as a model for human diseases. Many of these diseases involve monocytes and tissue macrophages in different states activation. Whilst methods vitro differentiation mouse from embryonic stem cells (ESC) bone marrow (BM) are well established, lacking the rat. gene expression profiles have also not been characterised to same extent mouse. We established methodology production ESC-derived compared their obtained lung peritoneal cavity those differentiated BM...
Autologous administration of attenuated Theileria parva-infected cells induces immunity to T. parva in cattle. The mechanism attenuation, however, is largely unknown. Here, we used RNA sequencing pathogenic and T-cells elucidate the transcriptional changes underpinning attenuation. We observed differential expression several host genes, including TRAIL, PD-1, TGF-β granzymes that are known regulate inflammation proliferation infected cells. Importantly, many genes linked with attenuation...
Acute stroke triggers extensive changes to myeloid immune cell populations in the brain that may be targets for limiting damage and enhancing repair. Immunomodulatory approaches will most effective with precise manipulation of discrete phenotypes time space. Here, we investigate how alters mononuclear composition at single-cell resolution key spatial patterns. Our results show multiple reactive microglial states monocyte-derived contribute an repertoire post-stroke brains. We identify...
Abstract Expression of Csf1r in adults is restricted to cells the macrophage lineage. Transgenic reporters based upon locus require inclusion highly conserved Fms-intronic regulatory element for expression. We have created Csf1r-EGFP transgenic sheep via lentiviral transgenesis a construct containing elements mouse and promoter. Committed bone marrow precursors blood monocytes express EGFP these animals. Sheep were divided into three populations, similar classical, intermediate, nonclassical...
Alcelaphine gammaherpesvirus 1 (AlHV-1) asymptomatically persists in its natural host, the wildebeest. However, cross-species transmission to cattle results induction of an acute and lethal peripheral T cell lymphoma-like disease (PTCL), named malignant catarrhal fever (MCF). Our previous findings demonstrated essential role for viral genome maintenance infected CD8
Abstract Sheep are a key source of meat, milk and fibre for the global livestock sector, an important biomedical model. Global analysis gene expression across multiple tissues has aided genome annotation supported functional mammalian genes. We present large-scale RNA-Seq dataset representing all major organ systems from adult sheep several juvenile, neonatal prenatal developmental time points. The Ovis aries reference (Oar v3.1) includes 27,504 genes (20,921 protein coding), which 25,350...
Abstract Microglia play key roles in brain homeostasis as well responses to neurodegeneration and neuroinflammatory processes caused by physical disease psychosocial stress. The pig is a physiologically relevant model species for studying human neurological disorders, many of which are associated with microglial dysfunction. Furthermore, pigs an important agricultural species, there need understand how function affects their welfare. As basis improved understanding enhance biomedical...
Abstract Background Infectious diseases of farmed and wild animals pose a recurrent threat to food security human health. The macrophage, key component the innate immune system, is first line defence against many infectious agents plays major role in shaping adaptive response. However, this phagocyte target host for pathogens. Understanding molecular basis interactions between macrophages pathogens therefore crucial development effective strategies combat important diseases. Results We...
Abstract Several different transgenic tamoxifen-inducible cre reporter lines have been used to analyse the contribution of embryonic precursors development mononuclear phagocyte system in mice. Here we show that tamoxifen treatment mother at 8.5dpc with doses commonly-used lineage trace studies produces a 4-5-fold expansion leukocyte populations by 10.5dpc, detected whole mounts embryos using Csf1r gene or separately expression Csf1r, Itgam (CD11b), Adgre1 (F4/80) Ptprc (CD45) mRNA. These...