A5011866704- Single-cell and spatial transcriptomics
- Renal and related cancers
- Neuroinflammation and Neurodegeneration Mechanisms
- Liver physiology and pathology
- Cell Image Analysis Techniques
- CRISPR and Genetic Engineering
- Retinal Development and Disorders
- Extracellular vesicles in disease
- Chronic Kidney Disease and Diabetes
- Cancer Cells and Metastasis
- Hippo pathway signaling and YAP/TAZ
- Inflammation biomarkers and pathways
- Epigenetics and DNA Methylation
- Gene Regulatory Network Analysis
- Fibroblast Growth Factor Research
- IL-33, ST2, and ILC Pathways
- Biomedical Ethics and Regulation
- Mosquito-borne diseases and control
- Advanced Proteomics Techniques and Applications
- Digestive system and related health
- Wnt/β-catenin signaling in development and cancer
- Renal cell carcinoma treatment
- Photochromic and Fluorescence Chemistry
- Genetic and Kidney Cyst Diseases
- Gastrointestinal motility and disorders
Novartis (Switzerland)
2007-2024
Novartis Institutes for BioMedical Research
2007-2022
SIB Swiss Institute of Bioinformatics
2021
University of Basel
2021
University of Zurich
2021
University Hospital of Basel
2021
Friedrich Miescher Institute
2019
Human organoids recapitulating the cell-type diversity and function of their target organ are valuable for basic translational research. We developed light-sensitive human retinal with multiple nuclear synaptic layers functional synapses. sequenced RNA 285,441 single cells from these at seven developmental time points periphery, fovea, pigment epithelium choroid light-responsive adult retinas, performed histochemistry. Cell types in matured vitro to a stable "developed" state rate similar...
Acute kidney injury (AKI) and chronic diseases are associated with high mortality morbidity. Although the underlying mechanisms determining transition from acute to not completely understood, immune-mediated processes critical in renal injury. We have performed a comparison of 2 mouse models leading either regeneration or fibrosis. Using global gene expression profiling we could identify immune-related pathways accounting for majority observed transcriptional changes during Unbiased...
Abstract Fibrosis is characterized by the excessive production of collagen and other extracellular matrix (ECM) components represents a leading cause morbidity mortality worldwide. Previous studies nonalcoholic steatohepatitis (NASH) with fibrosis were largely restricted to bulk transcriptome profiles. Thus, our understanding this disease limited an incomplete characterization liver cell types in general hepatic stellate cells (HSCs) particular, given that activated HSCs are major fibrogenic...
TREM2 is a transmembrane protein expressed exclusively in microglia the brain that regulates inflammatory responses to pathological conditions. Proteolytic cleavage of membrane affects microglial function and associated with Alzheimer's disease, but consequence reduced proteolytic has not been determined. Here, we generate transgenic mouse model Trem2 shedding (Trem2-Ile-Pro-Asp [IPD]) through amino-acid substitution an ADAM-protease recognition site. We show Trem2-IPD mice display increased...
We develop CellSIUS (Cell Subtype Identification from Upregulated gene Sets) to fill a methodology gap for rare cell population identification scRNA-seq data. outperforms existing algorithms specificity and selectivity types their transcriptomic signature in synthetic complex biological Characterization of human pluripotent differentiation protocol recapitulating deep-layer corticogenesis using reveals unrecognized complexity stem cell-derived cellular populations. enables novel populations...
Abstract Droplet-based single-cell omics, including RNA sequencing (scRNAseq), CRISPR perturbations (e.g., CROP-seq), and protein transcriptomic profiling (CITE-seq) hold great promise for comprehensive cell genetic screening at the resolution. However, these technologies suffer from substantial noise, among which ambient signals present in suspension may be predominant source. Current models to address this issue are highly technology-specific relatively scRNAseq-centric. while a universal...
Abstract Chemogenomic profiling is a powerful and unbiased approach to elucidate pharmacological targets the mechanism of bioactive compounds. Until recently, genome-wide, high-resolution experiments this nature have been limited fungal systems due lack mammalian genome-wide deletion collections. With example novel nicotinamide phosphoribosyltransferase (NAMPT) inhibitor, we demonstrate that CRISPR/Cas9 system enables generation transient homo- heterozygous libraries allows for...
Combination of functional epigenomics and single-cell CRISPR screens reveals that ER exerts its oncogenic role via downstream TFs.
<h3>Objective</h3> To identify an MS-specific immune cell population by deep phenotyping and relate it to soluble signaling molecules in CSF. <h3>Methods</h3> We analyzed surface expression of 22 markers paired blood/CSF samples from 39 patients using mass cytometry (cytometry time flight). also measured the concentrations 296 CSF proximity extension assay. Results were highly automated unsupervised algorithmic informatics. <h3>Results</h3> Mass objectively identified a B-cell characterized...
Summary How closely human organoids recapitulate cell-type diversity and maturation of their target organs is not well understood. We developed retinal with multiple nuclear synaptic layers. sequenced the RNA 158,844 single cells from these at six developmental time points periphery, fovea, pigment epithelium choroid light-responsive adult retinas, performed histochemistry. Cell types in matured vitro to a stable ‘developed’ state rate similar retina development vivo transcriptomes organoid...
How closely human organoids recapitulate cell-type diversity and maturation of their target organs is not well understood. We developed retinal with multiple nuclear synaptic layers. sequenced the RNA 158,844 single cells from these at six developmental time points periphery, fovea, pigment epithelium choroid light-responsive adult retinas, performed histochemistry. Cell types in matured vitro to a stable 'developed' state rate similar retina development vivo transcriptomes organoid cell...
Drug-induced gastrointestinal toxicity is a frequent clinical adverse event that needs to be carefully monitored and managed ensure patient compliance. While preclinical assessment of drug-induced mostly relies on animal experimentation, intestinal organoids have gained increasing attention identify toxicants in vitro. Nonetheless, current vitro protocols primarily assess structural alterations induced by drugs, whereas events can often stem from functional disturbances. Disruption serotonin...
Abstract Comprehensive benchmarking of computational methods for single-cell RNA sequencing (scRNA-seq) analysis is scarce. Using a modular workflow and large dataset with known cell composition, we benchmarked feature selection clustering methodologies scRNA-seq data. Results highlighted methodology gap rare population identification which developed CellSIUS ( Cell S ubtype Identification from U pregulated gene ets). outperformed existing approaches, enabled the populations and, in contrast...
Abstract Human organoids allow studying proliferation, lineage specification, and three-dimensional tissue development. Due to the inherent multicellular complexity, interrogation by systematic genetic methodologies is challenging. Here, we present first genome-wide CRISPR screen in iPSC-derived kidney organoids. The combination of genome editing, longitudinal sampling sorting specific cell populations enabled us uncover novel biology from development tubular morphogenesis. We validated high...
Summary TREM2 is a transmembrane protein expressed exclusively in microglia the brain that regulates inflammatory responses to pathological conditions. Proteolytic cleavage of membrane affects microglial function and associated with Alzheimer’s disease, but consequence reduced proteolytic has not been determined. We generated transgenic mouse model shedding (Trem2-IPD) through amino acid substitution ADAM-protease recognition site. found Trem2-IPD mice displayed increased cell surface...
Abstract Organoids recapitulate the self-organizing capacity of stem cells and tissue organization original organ in a controlled trackable environment. Intestinal organoids, particular, can develop from single cell into fully-grown structure that contains most types, patterns, morphogenetic properties adult intestine. Here we present protocol for high-throughput organoid culture multi-well plate format combined with high content immunofluorescence imaging RNA extraction. Our allows...