A5027645588- Single-cell and spatial transcriptomics
- Molecular Biology Techniques and Applications
- RNA modifications and cancer
- Cytokine Signaling Pathways and Interactions
- Tuberculosis Research and Epidemiology
- Cancer Genomics and Diagnostics
- Mycobacterium research and diagnosis
- Cancer-related molecular mechanisms research
- Ovarian cancer diagnosis and treatment
- Genomics and Chromatin Dynamics
- Analytical Methods in Pharmaceuticals
- Analytical Chemistry and Chromatography
- Immune cells in cancer
- MicroRNA in disease regulation
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- Immune Cell Function and Interaction
- Genomics and Phylogenetic Studies
- Cancer-related gene regulation
- Liver Disease Diagnosis and Treatment
- Biochemical effects in animals
- Cancer Immunotherapy and Biomarkers
- interferon and immune responses
- RNA and protein synthesis mechanisms
- Renal and related cancers
The University of Western Australia
2019-2024
Queen Elizabeth II Medical Centre
2019-2024
Harry Perkins Institute of Medical Research
2019-2024
Institute of Pharmacology Russian Academy of Medical Sciences
2018-2023
Massey University
2016-2022
Institute of Pharmacology
2019-2020
Russian Academy of Sciences
2020
Abstract Background Single-cell RNA sequencing has been widely adopted to estimate the cellular composition of heterogeneous tissues and obtain transcriptional profiles individual cells. Multiple approaches for optimal sample dissociation storage single cells have proposed as single-nuclei profiling methods. What lacking is a systematic comparison their relative biases benefits. Results Here, we compare gene expression single-cell suspensions prepared from adult mouse kidney using two tissue...
Abstract Development of high throughput single-cell sequencing technologies has made it cost-effective to profile thousands cells from diverse samples containing multiple cell types. To study how these different types work together, here we develop NATMI (Network Analysis Toolkit for Multicellular Interactions). uses connectomeDB2020 (a database 2293 manually curated ligand-receptor pairs with literature support) predict and visualise cell-to-cell communication networks (or bulk) expression...
Abstract High-grade serous ovarian carcinoma (HGSOC) is genetically unstable and characterised by the presence of subclones with distinct genotypes. Intratumoural heterogeneity linked to recurrence, chemotherapy resistance, poor prognosis. Here, we use spatial transcriptomics identify HGSOC study their association infiltrating cell populations. Visium reveals multiple tumour different copy number alterations present within individual sections. These differentially express various ligands...
Single-cell RNA sequencing (scRNA-seq) measures gene expression at the resolution of individual cells. Massively multiplexed single-cell profiling has enabled large-scale transcriptional analyses thousands cells in complex tissues. In most cases, true identity is unknown and needs to be inferred from transcriptomic data. Existing methods typically cluster (group) based on similarities their profiles assign same all within each using averaged levels. However, scRNA-seq experiments produce...
The incidence of hepatocellular carcinoma (HCC) is rapidly rising largely because increased obesity leading to nonalcoholic steatohepatitis (NASH), a known HCC risk factor. There are no approved treatments treat NASH. Here, we first used single-nucleus RNA sequencing characterize mouse model that mimics human NASH-driven HCC, the
Recent clinical successes have intensified interest in using adeno-associated virus (AAV) vectors for therapeutic gene delivery. The liver is a key target, given its critical physiological functions and involvement wide range of genetic diseases. In the present study, we first investigated validity xenograft mouse model repopulated with primary hepatocytes single-nucleus RNA sequencing (sn-RNA-seq) by studying transcriptomic profile human pre- post-engraftment. Complementary...
Tumor heterogeneity is a major obstacle to the success of cancer treatment. An accurate understanding and recognition tumor critical in clinical management patients. Here, we utilized single-cell RNA sequencing (scRNA-seq) uncover intra- intertumoral liver metastases from patient with metastatic uveal melanoma. The two analyzed were largely infiltrated by noncancerous cells significant variability proportion different cell types. Analysis copy-number variations (CNVs) showed gain 8q loss 6q...
Abstract Single-cell and single-nucleus RNA sequencing have been widely adopted in studies of heterogeneous tissues to estimate their cellular composition obtain transcriptional profiles individual cells. However, the current fragmentary understanding artefacts introduced by sample preparation protocols impedes selection optimal workflows compromises data interpretation. To bridge this gap, we compared performance several applied adult mouse kidneys. Our study encompasses two tissue...
T cell-based immunotherapies are a promising therapeutic approach for multiple malignancies, but their efficacy is limited by tumor hypoxia arising from dysfunctional blood vessels. Here, we report that cell-intrinsic properties of single vascular component, namely the pericyte, contribute to control oxygenation, macrophage polarization, vessel inflammation, and cell infiltration. Switching pericyte phenotype synthetic differentiated state reverses immune suppression sensitizes tumors...
Macrophages are sentinel cells essential for tissue homeostasis and host defence. Owing to their plasticity, macrophages acquire a range of functional phenotypes in response microenvironmental stimuli, which M(IFN-γ) M(IL-4/IL-13) well known opposing pro- anti-inflammatory roles. Enhancers have emerged as regulatory DNA elements crucial transcriptional activation gene expression. Using cap analysis expression epigenetic data, we identify on large-scale transcribed enhancers bone...
Tuberculosis is a life-threatening infectious disease caused by Mycobacterium tuberculosis (M.tb). M.tb subverts host immune responses to build favourable niche and survive inside of macrophages. Macrophages can control or eliminate the infection, if acquire appropriate functional phenotypes. Transcriptional regulation key process that governs activation maintenance these Among factors orchestrating transcriptional during enhancers still remain unexplored.We analysed transcribed in...
Using the Cap Analysis of Gene Expression (CAGE) technology, FANTOM5 consortium provided one most comprehensive maps transcription start sites (TSSs) in several species. Strikingly, ~72% them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Here, we probe these unassigned TSSs show that, all species studied, significant fraction CAGE peaks microsatellites, also called short tandem repeats (STRs). To confirm this transcription,...
Abstract High-grade serous ovarian carcinoma (HGSOC) is characterised by recurrence, chemotherapy resistance and overall poor prognosis. Genetic heterogeneity of tumour cells the microenvironment have been hypothesised as key determinants treatment relapse. Here, using a combination spatial single cell transcriptomics (10x Visium Chromium platforms), we examine genetic infiltrating populations HGSOC samples from eight patients with variable response to neoadjuvant chemotherapy. By inferring...
MicroRNAs (miRNAs), long non-coding RNAs (lncRNAs) and other functional (ncRNAs) have emerged as pivotal regulators involved in multiple biological processes. Recently, ncRNA control of gene expression has been identified a critical regulatory mechanism the immune system. Despite great efforts made to discover characterize ncRNAs, role for most remains unknown. To facilitate discoveries regulation system-related processes, we developed database immunologically relevant ncRNAs target genes...
Mammalian diversification has coincided with a rapid proliferation of various types noncoding RNAs, including members both snRNAs and snoRNAs. The significance this expansion however remains obscure. While some ncRNA copy-number expansions have been linked to functionally tractable effects, such events may equally likely be neutral, perhaps as result random retrotransposition. Hindering progress in our understanding observations is the difficulty establishing function for diverse features...
<title>Abstract</title> The normal developmental and homeostatic roles of tissue resident macrophages are subverted in tumor-associated to promote tumor progression. Pro-tumoral macrophage activities include immune evasion promotion invasion metastasis. We show that both regulated by the myeloid Src family kinase HCK, which drives motility invasive capacity. Loss HCK reduced growth aggressively Py8119 mammary 70–80% while excessive activity increased growth. Consistent with a role for...
Platinum-based chemotherapy in combination with anti-PD-L1 antibodies has shown promising results mesothelioma. However, the immunological mechanisms underlying its efficacy are not well understood and there no predictive biomarkers to guide treatment decisions. Here, we combine time course RNA sequencing (RNA-seq) of peripheral blood mononuclear cells pre-treatment tumor transcriptome data from single-arm, phase 2 DREAM trial (N = 54). Single-cell RNA-seq T cell receptor (TCR-seq) reveal that CD8
SUMMARY Current approaches to stage chronic liver diseases have limited utility directly predict cancer risk. Here, we employed single nucleus RNA sequencing (snRNA-seq) characterize the cellular microenvironment of healthy and chronically injured pre-malignant livers using two distinct mouse models. Analysis 40,748 hepatic nuclei unraveled a previously uncharacterized disease-associated hepatocyte transcriptional state (daHep). These cells were absent in livers, but increasingly prevalent...