A5087071718- Pancreatic function and diabetes
- Diabetes and associated disorders
- SARS-CoV-2 detection and testing
- Diabetes Management and Research
- Biosensors and Analytical Detection
- SARS-CoV-2 and COVID-19 Research
- Chromatin Remodeling and Cancer
- Cancer Mechanisms and Therapy
- Genomics and Phylogenetic Studies
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- RNA regulation and disease
- Cancer Genomics and Diagnostics
- Cancer-related gene regulation
- Metabolism, Diabetes, and Cancer
- Single-cell and spatial transcriptomics
- Viral Infections and Immunology Research
- Diet, Metabolism, and Disease
- Eosinophilic Disorders and Syndromes
- Lymphoma Diagnosis and Treatment
- RNA Research and Splicing
- interferon and immune responses
- Advanced biosensing and bioanalysis techniques
- Gastrointestinal Tumor Research and Treatment
- Immunotherapy and Immune Responses
Hebrew University of Jerusalem
2014-2024
Alzheimer's Association of Israel
2024
Hadassah Medical Center
2020-2023
iRobot (United States)
2020
Single-cell transcriptomics requires a method that is sensitive, accurate, and reproducible. Here, we present CEL-Seq2, modified version of our CEL-Seq method, with threefold higher sensitivity, lower costs, less hands-on time. We implemented CEL-Seq2 on Fluidigm's C1 system, providing its first single-cell, on-chip barcoding detected gene expression changes accompanying the progression through cell cycle in mouse fibroblast cells. also compare Smart-Seq to demonstrate CEL-Seq2's increased...
Abstract DNA methylation is a fundamental epigenetic mark that governs gene expression and chromatin organization, thus providing window into cellular identity developmental processes 1 . Current datasets typically include only fraction of sites are often based either on cell lines underwent massive changes in culture or tissues containing unspecified mixtures cells 2–5 Here we describe human methylome atlas, deep whole-genome bisulfite sequencing, allowing fragment-level analysis across...
Pooling multiple swab samples before RNA extraction and real-time reverse transcription polymerase chain reaction (RT-PCR) analysis has been proposed as a strategy to reduce costs increase throughput of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) tests. However, reports on practical large-scale group testing for SARS-CoV-2 have scant. Key open questions concern reduced sensitivity due sample dilution, the rate false positives, actual efficiency (number tests saved by...
How organ size and form are controlled during development is a major question in biology. Blood vessels have been shown to be essential for early of the liver pancreas, fundamental normal pathological tissue growth. Here, we report that, surprisingly, non-nutritional signals from blood act restrain pancreas Elimination endothelial cells increases embryonic pancreatic buds. Conversely, VEGF-induced hypervascularization decreases size. The growth phenotype results vascular restriction tip cell...
The molecular program underlying infrequent replication of pancreatic β-cells remains largely inaccessible. Using transgenic mice expressing green fluorescent protein in cycling cells, we sorted live, replicating and determined their transcriptome. Replicating upregulate hundreds proliferation-related genes, along with many novel putative cell cycle components. Strikingly, genes involved β-cell functions, namely, glucose sensing insulin secretion, were repressed. Further studies using...
A major hypothesis for the etiology of type 1 diabetes (T1D) postulates initiation by viral infection, leading to double-stranded RNA (dsRNA)-mediated interferon response and inflammation; however, a causal virus has not been identified. Here, we use mouse model, corroborated with human islet data, demonstrate that endogenous dsRNA in beta cells can lead diabetogenic immune response, thus identifying virus-independent mechanism T1D initiation. We found disruption editing enzyme adenosine...
Understanding the molecular triggers of pancreatic β-cell proliferation may facilitate development regenerative therapies for diabetes. Genetic studies have demonstrated an important role cyclin D2 in and mass homeostasis, but its specific function division mechanism regulation remain unclear. Here, we report that is present at high levels nucleus quiescent β-cells vivo. The major regulator expression glucose, acting via glycolysis calcium channels to control mRNA levels. Furthermore,...
Type 1 diabetes (T1D) is an autoimmune disease where pancreatic β-cells are destroyed by islet-infiltrating T cells. Although a role for β-cell defects has been suspected, abnormalities difficult to demonstrate. We show DNA damage response (DDR), presented activation of the 53BP1 protein and accumulation p53, in biopsy autopsy material from patients with recently diagnosed T1D as well rat model human T1D. The DDR more frequent islets infiltrated CD45+ immune cells, suggesting link islet...
Highlights•Mouse pancreatic acinar and beta cells grow dramatically during postnatal life•Acinar cell growth is a major contributor to pancreas in mice•Postnatal of the human relies entirely on increased number•Acinar size inversely correlates with lifespan among 24 mammalian speciesSummaryDevelopmental processes different mammals are thought share fundamental cellular mechanisms. We report dramatic increase development rodents, accounting for much organ after birth. Hypertrophy involves...
Blood cell counts often fail to report on immune processes occurring in remote tissues. Here, we use type-specific methylation patterns circulating cell-free DNA (cfDNA) for studying human dynamics. We characterized cfDNA released from specific types healthy individuals (N = 242), cross sectionally and longitudinally. Immune levels had no individual steady state as opposed blood counts, suggesting that concentration reflects adjustment of survival maintain homeostatic numbers. also observed...
Assessment of pancreas cell type composition is crucial to the understanding genesis diabetes. Current approaches use immunodetection protein markers, for example, insulin as a marker β-cells. A major limitation these methods that content varies in physiological and pathological conditions, complicating extrapolation actual number. Here, we demonstrate type–specific DNA methylation markers determining fraction specific types human islet specimens. We identified genomic loci are uniquely...
Abstract Testing for active SARS-CoV-2 infection is a fundamental tool in the public health measures taken to control COVID-19 pandemic. Due overwhelming use of RT-PCR tests worldwide, availability test kits has become major bottleneck. Here we demonstrate pooling strategies perform RNA extraction and pools, significantly increasing throughput while maintaining clinical sensitivity. We implemented method routine diagnosis setting asymptomatic populations, already tested 5,464 individuals...
Circulating cell-free DNA (cfDNA) fragments are a biological analyte with extensive utility in diagnostic medicine. Understanding the source of cfDNA and mechanisms release is crucial for designing interpreting cfDNA-based liquid biopsy assays. Using cell type-specific methylation markers as well genome-wide analysis, we determine that megakaryocytes, precursors anuclear platelets, major contributors to (~26%), while erythroblasts contribute 1-4% healthy individuals. Surprisingly, discover...
Abstract DNA methylation is a fundamental epigenetic mark that governs chromatin organization, cell identity, and gene expression. Here we describe human methylome atlas, based on deep whole-genome bisulfite sequencing allowing fragment-level analysis across thousands of unique markers for 39 types sorted from 207 healthy tissue samples. Replicates the same cell-type are >99.5% identical, demonstrating robustness identity programs to genetic variation environmental perturbation....
Most of our knowledge on cell kinetics stems from in vitro studies continuously dividing cells. In this study, we determine vivo cell-cycle parameters pancreatic β-cells, a largely quiescent population, using drugs that mimic or prevent glucose-induced replication β-cells mice. Quiescent exposed to mitogenic glucose stimulation require 8 h enter the G1 phase cycle, and time is prolonged older age. The duration G1, S, G2/M ∼5, 8, 6 h, respectively. We further provide first demonstration...
Constitutive expression of active Akt (Akttg) drives hyperplasia and hypertrophy pancreatic β-cells, concomitantly with increased insulin secretion improved glucose tolerance, at a later stage the development insulinoma. To determine which functions are mediated by ribosomal protein S6 (rpS6), an effector, we generated mice that express constitutive in β-cells background unphosphorylatable (rpS6P-/-). rpS6 phosphorylation deficiency failed to block Akttg-induced aneuploidy as well...
Abstract Senescent cells can influence the function of tissues in which they reside, and their propensity for disease. A portion adult human pancreatic beta express senescence marker p16, yet it is unclear whether are a senescent state, how this affects insulin secretion. We analyzed single-cell transcriptome datasets cells, found that p16-positive gene signatures, as well elevated levels beta-cell maturation genes, consistent with enhanced functionality. beta-like culture undergo chromatin...