A5029759213- Single-cell and spatial transcriptomics
- Liver physiology and pathology
- Gut microbiota and health
- Cancer Cells and Metastasis
- RNA Research and Splicing
- Caveolin-1 and cellular processes
- Inflammatory Bowel Disease
- Colorectal Cancer Screening and Detection
- Advanced Proteomics Techniques and Applications
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Genetic factors in colorectal cancer
- Digestive system and related health
- Kruppel-like factors research
- Tendon Structure and Treatment
- MicroRNA in disease regulation
- IL-33, ST2, and ILC Pathways
- Cancer Genomics and Diagnostics
- Liver Disease Diagnosis and Treatment
- Influenza Virus Research Studies
- interferon and immune responses
- Barrier Structure and Function Studies
- Pancreatic and Hepatic Oncology Research
- Microscopic Colitis
- Machine Learning in Bioinformatics
Weizmann Institute of Science
2016-2023
Host shutoff is a common strategy used by viruses to repress cellular mRNA translation and concomitantly allow the efficient of viral mRNAs. Here we use RNA-sequencing ribosome profiling explore mechanisms that are being utilized Influenza A virus (IAV) induce host shutoff. We show transcripts not preferentially translated instead decline in protein synthesis mediated takeover on pool. Our measurements also uncover strong variability levels reduction, revealing short less affected IAV....
The intestinal epithelium is largely maintained by self-renewing stem cells but with apparently committed progenitors also contributing, particularly following tissue damage. However, the mechanism of, and requirement for, progenitor plasticity in mediating pathological response remain unknown. Here we show that phosphorylation of transcription factor Atoh1 required for both contribution secretory to cell pool a robust regenerative response. As confirmed lineage tracing, Atoh1+...
Single-cell transcriptomics (scRNA-seq) has revolutionized the understanding of spatial architecture tissue structure and function. Advancing "transcript-centric" view scRNA-seq analyses is presently restricted by limited resolution proteomics genome-wide techniques to analyze post-translational modifications. Here, combining cell sorting with quantitative proteomics/phosphoproteomics, we established spatially resolved proteome landscape liver endothelium, yielding deep mechanistic insight...
The mechanical challenge of attaching elastic tendons to stiff bones is solved by the formation a unique transitional tissue. Here, we show that murine tendon-to-bone attachment cells are bi-fated, activating mixture chondrocyte and tenocyte transcriptomes, under regulation shared regulatory elements Krüppel-like factors (KLFs) transcription factors. High-throughput bulk single-cell RNA sequencing humeral revealed expression hundreds chondrogenic tenogenic genes, which was validated in situ...
Understanding protein distribution patterns across tissue architecture is crucial for deciphering organ function in health and disease. Here, we applied single-cell Deep Visual Proteomics to perform spatially-resolved proteome analysis of individual cells native tissue. We combined this with a novel strategic cell selection pipeline continuous gradient mapping framework investigate larger clinical cohorts. generated comprehensive spatial map the human hepatic by analyzing hundreds...
Abstract Tissue stem cells produce a constant flux of differentiated with distinct proportions. Here, we show that in colonic crypts differentiate early to form precisely 1:3 ratio secretory absorptive cells. This precision is surprising, as there are only eight making irreversible fate decisions, and so large stochastic effects this small pool should have yielded much larger noise cell We use single molecule FISH , lineage‐tracing mice simulations identify the homeostatic mechanisms...
Background & AimsNoninvasive modalities for assessing active endoscopic and histologic inflammation in Crohn’s disease ulcerative colitis patients are critically needed. Fecal wash host shed-cell transcriptomics has been shown to be a robust classifier of inflammatory bowel with distal colitis. Whether such fecal washes can inform on processes occurring more proximal intestinal segments is currently unknown.MethodsFifty-nine 50 controls were prospectively enrolled. Biopsy specimens from the...
Colonoscopy is the gold standard for evaluation of inflammation in inflammatory bowel diseases (IBDs), yet entails cumbersome preparations and risks injury. Existing non-invasive prognostic tools are limited their diagnostic power. Moreover, transcriptomics colonic biopsies have been inconclusive association with clinical features.To assess utility host faecal wash samples patients IBD compared controls.In this prospective cohort study, we obtained faecal-wash from controls undergoing lower...
The intestinal epithelium is a highly structured tissue composed of repeating crypt-villus units 1,2 . Enterocytes, which constitute the most abundant cell type, perform diverse tasks absorbing wide range nutrients while protecting body from harsh bacterial-rich environment. It unknown if these are equally performed by all enterocytes or whether they spatially zonated along villus axis 3 Here, we whole-transcriptome measurements laser-capture-microdissected segments to extract large panel...
Abstract The mammalian liver is composed of repeating hexagonal units termed lobules. Spatially-resolved single-cell transcriptomics revealed that about half hepatocyte genes are differentially expressed across the lobule. Technical limitations impede reconstructing similar global spatial maps other features. Here, we used zonated surface markers to sort hepatocytes from defined lobule zones with high resolution. We applied transcriptomics, microRNA array measurements and Mass-spectrometry...
SUMMARY The intestinal epithelium is maintained by a small number of self-renewing stem cells in homeostasis. In addition committed progenitors can contribute to the functional cell compartment at low level during homeostasis and substantially regeneration following tissue damage. However mechanism of, requirement for, progenitor plasticity mediating pathological response has not been demonstrated. Here we show that multisite phosphorylation transcription factor Atoh1 required both for...
Summary The liver carries a remarkable ability to regenerate rapidly after acute zonal damage. Single-cell approaches are necessary study this process, given the spatial heterogeneity of multiple cell types. Here, we use spatially-resolved single RNA sequencing (scRNAseq) dynamics mouse regeneration acetaminophen (APAP) intoxication. We find that hepatocytes proliferate throughout lobule, creating mitotic pressure required repopulate necrotic pericentral zone rapidly. A subset located at...
The intestine is lined with isolated lymphoid follicles (ILFs) that facilitate sampling of luminal antigens to elicit immune responses. Technical challenges related the scarcity and small sizes ILFs their follicle-associated epithelium (FAE) impeded characterization spatial gene expression programs. Here, we combined RNA sequencing laser capture microdissected tissues single-molecule transcript imaging obtain a map ILF its associated FAE in mouse intestine. We identified zonated programs...
Abstract The connection between different tissues is vital for the development and function of any organs systems. In musculoskeletal system, attachment elastic tendons to stiff bones poses a mechanical challenge that solved by formation transitional tissue, which allows transfer muscle forces skeleton without tearing. Here, we show tendon-to-bone cells are bi-fated, activating mixture chondrocyte tenocyte transcriptomes, regulated sharing regulatory elements with these Krüppel-like factors...
Abstract Background Non-invasive modalities for assessing active endoscopic and histological inflammation in Crohn’s disease Ulcerative Colitis patients are critically needed. Fecal wash host transcriptomics has been shown to be a robust classifier of inflammatory bowel (IBD) with distal colitis. Whether such fecal washes can inform on processes occurring more proximal intestinal segments is currently unknown. Methods Crohn's as well healthy controls were prospectively enrolled. Host...