A5050267398- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Mosquito-borne diseases and control
- Immune cells in cancer
- Immune Response and Inflammation
- Viral Infections and Vectors
- Single-cell and spatial transcriptomics
- Tuberculosis Research and Epidemiology
- Allergic Rhinitis and Sensitization
- Diabetes and associated disorders
- Epigenetics and DNA Methylation
- RNA and protein synthesis mechanisms
- Mast cells and histamine
- Genomics and Phylogenetic Studies
- Phagocytosis and Immune Regulation
- Bioinformatics and Genomic Networks
- Cytomegalovirus and herpesvirus research
- HIV Research and Treatment
- Neuroinflammation and Neurodegeneration Mechanisms
- Insect symbiosis and bacterial influences
- Gene expression and cancer classification
- Influenza Virus Research Studies
- Asthma and respiratory diseases
- Cancer-related molecular mechanisms research
Singapore Immunology Network
2013-2022
Agency for Science, Technology and Research
2013-2022
Royal Children's Hospital
2020-2022
Murdoch Children's Research Institute
2020-2022
Institute of Bioinformatics
2019
Jena University Hospital
2018
Singapore Institute for Clinical Sciences
2017
National University of Singapore
2014-2016
Genome Institute of Singapore
2014
Johnson & Johnson (United States)
2009-2014
Tissue macrophages have a split personality Resident tissue (RTMs) reside in various tissue-specific niches during development. They evince microenvironment-directed phenotypes that support host defense and homeostasis. Chakarov et al. used single-cell RNA sequencing fate-mapping of murine lung RTMs to interrogate RTM-subset heterogeneity, interrelationships, ontogeny (see the Perspective by Mildner Yona). In addition alveolar macrophages, they identified two different interstitial...
The molecular characterization of immune subsets is important for designing effective strategies to understand and treat diseases. We characterized 29 cell types within the peripheral blood mononuclear (PBMC) fraction healthy donors using RNA-seq (RNA sequencing) flow cytometry. Our dataset was used, first, identify sets genes that are specific, co-expressed, have housekeeping roles across types. Then, we examined differences in mRNA heterogeneity abundance revealing type specificity. Last,...
Mouse and human dendritic cells (DCs) are composed of functionally specialized subsets, but precise interspecies correlation is currently incomplete. Here, we showed that murine lung gut lamina propria CD11b+ DC populations were comprised two subsets: FLT3- IRF4-dependent CD24+CD64− DCs contaminating CSF-1R-dependent CD24−CD64+ macrophages. Functionally, loss CD24+CD11b+ abrogated CD4+ T cell-mediated interleukin-17 (IL-17) production in steady state after Aspergillus fumigatus challenge....
Dendritic cells (DCs) are professional antigen-presenting that hold great therapeutic potential. Multiple DC subsets have been described, and it remains challenging to align them across tissues species analyze their function in the absence of macrophage contamination. Here, we provide validate a universal toolbox for automated identification DCs through unsupervised analysis conventional flow cytometry mass data obtained from multiple mouse, macaque, human tissues. The use minimal set...
Abstract The increasing volume of ChIP-chip and ChIP-seq data being generated creates a challenge for standard, integrative reproducible bioinformatics analysis platforms. We developed web-based application called Cistrome, based on the Galaxy open source framework. In addition to standard functions, Cistrome has 29 ChIP-chip- ChIP-seq-specific tools in three major categories, from preliminary peak calling correlation analyses downstream genome feature association, gene expression analyses,...
Dendritic cell (DC)-mediated cross-presentation of exogenous antigens acquired in the periphery is critical for initiation CD8(+) T responses. Several DC subsets are described human tissues but migratory cross-presenting DCs have not been isolated, despite their potential importance immunity to pathogens, vaccines, and tumors tolerance self. Here, we identified a CD141(hi) present interstitial dermis, liver, lung that was distinct from majority CD1c(+) CD14(+) tissue superior at soluble...
Microglia are embryonically seeded macrophages that contribute to brain development, homeostasis, and pathologies. It is thus essential decipher how microglial properties temporally regulated by intrinsic extrinsic factors, such as sexual identity the microbiome. Here, we found microglia undergo differentiation phases, discernable transcriptomic signatures chromatin accessibility landscapes, which can diverge in adult males females. Remarkably, absence of microbiome germ-free mice had a time...
Dendritic cells (DC) are professional antigen-presenting that orchestrate immune responses. The human DC population comprises two main functionally specialized lineages, whose origins and differentiation pathways remain incompletely defined. Here, we combine high-dimensional technologies-single-cell messenger RNA sequencing (scmRNAseq) cytometry by time-of-flight (CyTOF)-to identify blood CD123+CD33+CD45RA+ precursors (pre-DC). Pre-DC share surface markers with plasmacytoid (pDC) but have...
The global burden of tuberculosis (TB) morbidity and mortality remains immense. A potential new approach to TB therapy is augment protective host immune responses. We report that the antidiabetic drug metformin (MET) reduces intracellular growth Mycobacterium (Mtb) in an AMPK (adenosine monophosphate-activated protein kinase)-dependent manner. MET controls drug-resistant Mtb strains, increases production mitochondrial reactive oxygen species, facilitates phagosome-lysosome fusion. In...
Single-cell mass cytometry significantly increases the dimensionality of analysis as compared to fluorescence flow cytometry, providing unprecedented resolution cellular diversity in tissues. However, and interpretation these high-dimensional data poses a significant technical challenge. Here, we present cytofkit, new Bioconductor package, which integrates both state-of-the-art bioinformatics methods in-house novel algorithms offer comprehensive toolset for analysis. Cytofkit provides...
Dendritic cells (DCs), monocytes, and macrophages are leukocytes with critical roles in immunity tolerance. The DC network is evolutionarily conserved; the homologs of human tissue CD141hiXCR1+CLEC9A+ DCs CD1c+ murine CD103+ CD64−CD11b+ DCs. In addition, tissues also contain CD14+ cells, currently designated as DCs, an as-yet unknown counterpart. Here we have demonstrated that dermal a tissue-resident population monocyte-derived short half-life <6 days. decline reconstitution kinetics blood...
Flow cytometry (FCM) is widely used in both clinical and basic research to characterize cell phenotypes functions. The latest FCM instruments analyze up 20 markers of individual cells, producing high-dimensional data. This requires the use clustering dimensionality reduction techniques automatically segregate sub-populations an unbiased manner. However, automated analyses may lead false discoveries due inter-sample differences quality properties.We present R package, flowAI, containing two...
Gut microbes live in symbiosis with their hosts, but how mutualistic animal-microbe interactions emerge is not understood. By adaptively evolving the opportunistic fungal pathogen Candida albicans mouse gastrointestinal tract, we selected strains that only had lost main virulence program also protected new hosts against a variety of systemic infections. This protection was independent adaptive immunity, arose as early single day postpriming, dependent on increased innate cytokine responses,...
Abstract Human dendritic cells (DCs) regulate the balance between immunity and tolerance through selective activation by environmental pathogen-derived triggers. To characterize rapid changes that occur during this process, we analyzed underlying metabolic activity across a spectrum of functional DC states, from immunogenic to tolerogenic. We found in contrast pronounced proinflammatory program mature DCs, tolerogenic DCs displayed markedly augmented catabolic pathway, related oxidative...