A5033187875- Single-cell and spatial transcriptomics
- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- IL-33, ST2, and ILC Pathways
- Immune Cell Function and Interaction
- Cancer Genomics and Diagnostics
- T-cell and B-cell Immunology
- Neonatal Respiratory Health Research
- Immune responses and vaccinations
- Congenital gastrointestinal and neural anomalies
- Congenital heart defects research
- Developmental Biology and Gene Regulation
- Long-Term Effects of COVID-19
- Adipose Tissue and Metabolism
- Respiratory viral infections research
- Receptor Mechanisms and Signaling
- RNA Research and Splicing
- Immunotherapy and Immune Responses
- Congenital Diaphragmatic Hernia Studies
- Nasal Surgery and Airway Studies
- Renal cell carcinoma treatment
- Cell Image Analysis Techniques
- Muscle Physiology and Disorders
- interferon and immune responses
- T-cell and Retrovirus Studies
Wellcome Sanger Institute
2020-2025
Genomics England
2022
United States Army Medical Research Institute of Infectious Diseases
1981
Despite their crucial role in health and disease, our knowledge of immune cells within human tissues remains limited. We surveyed the compartment 16 from 12 adult donors by single-cell RNA sequencing VDJ generating a dataset ~360,000 cells. To systematically resolve cell heterogeneity across tissues, we developed CellTypist, machine learning tool for rapid precise type annotation. Using this approach, combined with detailed curation, determined tissue distribution finely phenotyped types,...
Thymus development, cell by The human thymus is the organ responsible for maturation of many types T cells, which are immune cells that protect us from infection. However, it not well known how these develop with a full complement contains necessary variation to variety pathogens. By performing single-cell RNA sequencing on more than 250,000 Park et al. examined changes occur in over course life. They found development occurs coordinated manner among and their developmental microenvironment....
Abstract The cellular landscape of the human intestinal tract is dynamic throughout life, developing in utero and changing response to functional requirements environmental exposures. Here, comprehensively map cell lineages, we use single-cell RNA sequencing antigen receptor analysis almost half a million cells from up 5 anatomical regions 11 distinct healthy paediatric adult gut. This reveals existence transcriptionally BEST4 epithelial tract. Furthermore, implicate IgG sensing as function...
ABSTRACT The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, creates an urgent need for identifying molecular mechanisms that mediate viral entry, propagation, and tissue pathology. Cell membrane bound angiotensin-converting enzyme 2 (ACE2) associated proteases, transmembrane protease serine (TMPRSS2) Cathepsin L (CTSL), were previously identified as mediators of SARS-CoV2 cellular entry. Here, we assess cell type-specific RNA expression ACE2 , TMPRSS2 CTSL through integrated...
It is not fully understood why COVID-19 typically milder in children
The function of a cell is defined by its intrinsic characteristics and niche: the tissue microenvironment in which it dwells. Here we combine single-cell spatial transcriptomics data to discover cellular niches within eight regions human heart. We map cells microanatomical locations integrate knowledge-based unsupervised structural annotations. also profile cardiac conduction system
We present a multiomic cell atlas of human lung development that combines single-cell RNA and ATAC sequencing, high-throughput spatial transcriptomics, imaging. Coupling methods with analysis has allowed comprehensive cellular survey the epithelial, mesenchymal, endothelial, erythrocyte/leukocyte compartments from 5–22 post-conception weeks. identify previously uncharacterized states in all compartments. These include developmental-specific secretory progenitors subtype neuroendocrine...
Tumor behavior is intricately dependent on the oncogenic properties of cancer cells and their multi-cellular interactions. To understand these dependencies within wider microenvironment, we studied over 270,000 single-cell transcriptomes 100 microdissected whole exomes from 12 patients with kidney tumors, prior to validation using spatial transcriptomics. Tissues were sampled multiple regions tumor core, tumor-normal interface, normal surrounding tissues, peripheral blood. We find that...
Abstract Single-cell transcriptomics has allowed unprecedented resolution of cell types/states in the human lung, but their spatial context is less well defined. To (re)define tissue architecture lung and airways, we profiled five proximal-to-distal locations healthy lungs depth using multi-omic single cell/nuclei (queryable at lungcellatlas.org ). Using computational data integration analysis, extend beyond suspension paradigm discover macro micro-anatomical compartments including...
Abstract Human limbs emerge during the fourth post-conception week as mesenchymal buds, which develop into fully formed over subsequent months 1 . This process is orchestrated by numerous temporally and spatially restricted gene expression programmes, making congenital alterations in phenotype common 2 Decades of work with model organisms have defined fundamental mechanisms underlying vertebrate limb development, but an in-depth characterization this humans has yet to be performed. Here we...
The COVID-19 pandemic is an ongoing global health threat, yet our understanding of the dynamics early cellular responses to this disease remains limited
Skeletal muscle aging is a key contributor to age-related frailty and sarcopenia with substantial implications for global health. Here we profiled 90,902 single cells 92,259 nuclei from 17 donors map the process in adult human intercostal muscle, identifying cellular changes each compartment. We found that distinct subsets of stem exhibit decreased ribosome biogenesis genes increased CCL2 expression, causing different phenotypes. Our atlas also highlights an expansion associated...
Abstract Children infected with SARS-CoV-2 rarely progress to respiratory failure. However, the risk of mortality in people over 85 years age remains high. Here we investigate differences cellular landscape and function paediatric (<12 years), adult (30–50 years) older (>70 ex vivo cultured nasal epithelial cells response infection SARS-CoV-2. We show that cell tropism SARS-CoV-2, expression ACE2 TMPRSS2 subtypes, differ between groups. While ciliated are viral replication centres...
The immune system comprises multiple cell lineages and heterogeneous subsets found in blood tissues throughout the body. While human responses differ between sites over age, underlying sources of variation remain unclear as most studies are limited to peripheral blood. Here, we took a systems approach comprehensively profile RNA surface protein expression 1.25 million cells isolated from blood, lymphoid organs, mucosal 24 organ donors aged 20-75 years. We applied multimodal classifier...
Summary Multiple distinct cell types of the human lung and airways have been defined by single RNA sequencing (scRNAseq). Here we present a multi-omics spatial atlas to define novel which map back into macro- micro-anatomical tissue context functional microenvironments. Firstly, generated nuclei sequencing, VDJ-sequencing Visium Spatial Transcriptomics data sets from 5 different locations airways. Secondly, additional types/states, as well spatially known airway types, such adult...
Abstract The COVID-19 pandemic is an ongoing global health threat, yet our understanding of the cellular disease dynamics remains limited. In unique human challenge study we used single cell genomics nasopharyngeal swabs and blood to temporally resolve abortive, transient sustained infections in 16 seronegative individuals challenged with preAlpha-SARS-CoV-2. Our analyses revealed rapid changes type proportions dozens highly dynamic response states epithelial immune cells associated specific...
Abstract We present a multiomic cell atlas of human lung development that combines single RNA and ATAC sequencing, high throughput spatial transcriptomics imaging. Coupling methods with analysis has allowed comprehensive cellular survey the epithelial, mesenchymal, endothelial erythrocyte/leukocyte compartments from 5-22 post conception weeks. identify new states in all compartments. These include developmental-specific secretory progenitors subtype neuroendocrine related to small cancer....
Abstract A cell’s function is defined by its intrinsic characteristics and niche: the tissue microenvironment in which it dwells. Here, we combine single-cell spatial transcriptomic data to discover cellular niches within eight regions of human heart. We map cells micro-anatomic locations integrate knowledge-based unsupervised structural annotations. For first time, profile cardiac conduction system, revealing their distinctive repertoire ion channels, G-protein coupled receptors, cell...
Abstract The cellular landscape of the human intestinal tract is dynamic throughout life, developing in utero and changing response to functional requirements environmental exposures. To comprehensively map cell lineages healthy developing, pediatric adult gut from ten distinct anatomical regions, as well draining lymph nodes, we used singlecell RNA-seq VDJ analysis roughly one third a million cells. This reveals presence BEST4+ absorptive cells tract, demonstrating existence this type...
Abstract Human limbs emerge during the fourth post-conception week as mesenchymal buds which develop into fully-formed over subsequent months. Limb development is orchestrated by numerous temporally and spatially restricted gene expression programmes, making congenital alterations in phenotype common. Decades of work with model organisms has outlined fundamental processes underlying vertebrate limb development, but an in-depth characterisation this process humans yet to be performed. Here we...
Abstract Skeletal muscle ageing increases the incidence of age-associated frailty and sarcopenia in elderly worldwide, leading to increased morbidity mortality. However, our understanding cellular molecular mechanisms is still far from complete. Here, we generate a single-cell single-nucleus transcriptomic atlas skeletal 15 donors across adult human lifespan, accompanied by myofiber typing using imaging. Our reveals acting different compartments muscle, including stem cells (MuSCs),...