A5042603268- Single-cell and spatial transcriptomics
- Neuroinflammation and Neurodegeneration Mechanisms
- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Immune cells in cancer
- Immunotherapy and Immune Responses
- RNA modifications and cancer
- Gene Regulatory Network Analysis
- Pancreatic function and diabetes
- Cell Image Analysis Techniques
- Diet, Metabolism, and Disease
- Immune Cell Function and Interaction
- Glioma Diagnosis and Treatment
- Cancer, Stress, Anesthesia, and Immune Response
- Bioinformatics and Genomic Networks
- Diabetes and associated disorders
- Cancer Genomics and Diagnostics
- interferon and immune responses
- Biochemical Analysis and Sensing Techniques
- Clostridium difficile and Clostridium perfringens research
- Cardiac, Anesthesia and Surgical Outcomes
- Homicide, Infanticide, and Child Abuse
- Intimate Partner and Family Violence
- CAR-T cell therapy research
- Fibroblast Growth Factor Research
Salk Institute for Biological Studies
2016-2025
University of California, San Diego
2019
University of Minnesota
2019
Highland Hospital
1994
Of mice and men's microglia Microglia are immune system cells that function in protecting maintaining the brain. Gosselin et al. examined epigenetics RNA transcripts from single microglial observed consistent profiles among samples despite differences age, sex, diagnosis. Mouse human demonstrated similar microglia-specific gene expression profiles, as well a shared environmental response collected either immediately after surgery (ex vivo) or culturing (in vitro). Interestingly, those genes...
Noncoding genetic variation is a major driver of phenotypic diversity, but functional interpretation challenging. To better understand common associated with brain diseases, we defined noncoding regulatory regions for cell types the human brain. Whereas psychiatric disorders were primarily variants in transcriptional enhancers and promoters neurons, sporadic Alzheimer's disease (AD) largely confined to microglia enhancers. Interactome maps connecting disease-risk cell-type-specific revealed...
Abstract Single-cell sequencing methods have emerged as powerful tools for identification of heterogeneous cell types within defined brain regions. Application single-cell techniques to study the transcriptome activated neurons can offer insight into molecular dynamics associated with differential neuronal responses a given experience. Through evaluation common whole-cell and single-nuclei RNA-sequencing (snRNA-seq) methods, here we show that snRNA-seq faithfully recapitulates...
Abstract Mammalian brain cells show remarkable diversity in gene expression, anatomy and function, yet the regulatory DNA landscape underlying this extensive heterogeneity is poorly understood. Here we carry out a comprehensive assessment of epigenomes mouse cell types by applying single-nucleus methylation sequencing 1,2 to profile 103,982 nuclei (including 95,815 neurons 8,167 non-neuronal cells) from 45 regions cortex, hippocampus, striatum, pallidum olfactory areas. We identified 161...
Abstract Single-cell DNA methylome profiling has enabled the study of epigenomic heterogeneity in complex tissues and during cellular reprogramming. However, broader applications method have been impeded by modest quality sequencing libraries. Here we report snmC-seq2, which provides improved read mapping, reduced artifactual reads, enhanced throughput, as well increased library complexity coverage uniformity compared to snmC-seq. snmC-seq2 is an efficient strategy suited for large-scale...
Delineating the gene-regulatory programs underlying complex cell types is fundamental for understanding brain function in health and disease. Here, we comprehensively examined human epigenomes by probing DNA methylation chromatin conformation at single-cell resolution 517 thousand cells (399 neurons 118 non-neurons) from 46 regions of three adult male brains. We identified 188 characterized their molecular signatures. Integrative analyses revealed concordant changes methylation,...
Cytosine DNA methylation is essential in brain development and implicated various neurological disorders. Understanding diversity across the entire a spatial context fundamental for complete molecular atlas of cell types their gene regulatory landscapes. Here we used single-nucleus methylome sequencing (snmC-seq3) multi-omic (snm3C-seq)
Altered transcriptional and epigenetic regulation of brain cell types may contribute to cognitive changes with advanced age. Using single-nucleus multi-omic DNA methylation transcriptome sequencing (snmCT-seq) in frontal cortex from young adult aged donors, we found widespread age- sex-related variation specific neuron types. The proportion inhibitory SST- VIP-expressing neurons was reduced donors. Excitatory had more profound age-related their gene expression than cells. Hundreds genes...
Sickness-induced anorexia is a conserved behavior induced during infections. Here, we report that an intestinal pathogen, Salmonella Typhimurium, inhibits by manipulating the gut-brain axis. Inhibition of inflammasome activation S. Typhimurium effector, SlrP, prevented caused IL-1β-mediated signaling to hypothalamus via vagus nerve. Rather than compromising host defenses, pathogen-mediated inhibition increased survival. SlrP-mediated invasion and systemic infection wild-type reducing...
Abstract Neuronal cell types are classically defined by their molecular properties, anatomy and functions. Although recent advances in single-cell genomics have led to high-resolution characterization of type diversity the brain 1 , neuronal often studied out context anatomical properties. To improve our understanding relationship between features that define cortical neurons, here we combined retrograde labelling with single-nucleus DNA methylation sequencing link neural epigenomic...
Like other complex multicellular organisms, plants are composed of different cell types with specialized shapes and functions. For example, most laminar leaves consist multiple photosynthetic types. These include the palisade mesophyll, which typically forms one or more layers on adaxial side leaf. Despite their importance for photosynthesis, we know little about how cells differ at molecular level from To this end, have used a combination cell-specific profiling using fluorescence-activated...
Abstract Single-cell analyses parse the brain’s billions of neurons into thousands ‘cell-type’ clusters residing in different brain structures 1 . Many cell types mediate their functions through targeted long-distance projections allowing interactions between specific types. Here we used epi-retro-seq 2 to link single-cell epigenomes and for 33,034 dissected from 32 regions projecting 24 targets (225 source-to-target combinations) across whole mouse brain. We highlight uses these data...
Microglia phenotypes are highly regulated by the brain environment, but transcriptional networks that specify maturation of human microglia poorly understood. Here, we characterized stage-specific transcriptomes and epigenetic landscapes fetal postnatal acquired corresponding data in induced pluripotent stem cell (iPSC)-derived microglia, cerebral organoids, following engraftment into humanized mice. Parallel development computational approaches considered transcription factor (TF)...
Chronic pancreatitis, a known risk factor for the development of pancreatic ductal adenocarcinoma (PDA), is serious, widespread medical condition characterized by inflammation, fibrosis and acinar to metaplasia (ADM). ADM cell type transdifferentiation event where cells become ductal-like under conditions injury or oncogenic mutation. Here, we show that chronic pancreatitis in genetically wild mice results formation significant population chemosensory tuft cells. Transcriptomic analyses...
Cytosine DNA methylation is essential in brain development and has been implicated various neurological disorders. A comprehensive understanding of diversity across the entire context brain's 3D spatial organization for building a complete molecular atlas cell types their gene regulatory landscapes. To this end, we employed optimized single-nucleus methylome (snmC-seq3) multi-omic (snm3C-seq
Abstract Higher-order chromatin structure and DNA methylation are critical for gene regulation, but how these vary across the human body remains unclear. We performed multi-omic profiling of 3D genome 86,689 single nuclei 16 tissues, identifying 35 major 206 cell subtypes. revealed extensive changes in CG non-CG almost all types characterized at an unprecedented cellular resolution. Intriguingly, discrepancies exist between delineated by structure, indicating that role distinct epigenomic...