Davide Capauto
A5075418930- RNA Research and Splicing
- Single-cell and spatial transcriptomics
- Genomics and Chromatin Dynamics
- RNA and protein synthesis mechanisms
- MicroRNA in disease regulation
- Amyotrophic Lateral Sclerosis Research
- Circular RNAs in diseases
- Seed Germination and Physiology
- Autism Spectrum Disorder Research
- Bioinformatics and Genomic Networks
- Plant Molecular Biology Research
- Light effects on plants
- Tryptophan and brain disorders
- Epigenetics and DNA Methylation
- Congenital heart defects research
- Neurogenetic and Muscular Disorders Research
- Pluripotent Stem Cells Research
- Cancer-related molecular mechanisms research
- Genetic Associations and Epidemiology
- Plant Genetic and Mutation Studies
- Genomic variations and chromosomal abnormalities
- Gene Regulatory Network Analysis
- Genetics, Aging, and Longevity in Model Organisms
- Mitochondrial Function and Pathology
- Gut microbiota and health
Yale University
2020-2024
Sapienza University of Rome
2014-2023
University of New Haven
2023
Italian Institute of Technology
2017-2018
Istituto Pasteur
2014
Abstract The RNA-binding protein FUS participates in several RNA biosynthetic processes and has been linked to the pathogenesis of amyotrophic lateral sclerosis (ALS) frontotemporal dementia. Here we report that controls back-splicing reactions leading circular (circRNA) production. We identified circRNAs expressed vitro -derived mouse motor neurons (MNs) determined production a considerable number these is regulated by FUS. Using RNAi overexpression wild-type ALS-associated mutants,...
Single-cell genomics is a powerful tool for studying heterogeneous tissues such as the brain. Yet little understood about how genetic variants influence cell-level gene expression. Addressing this, we uniformly processed single-nuclei, multiomics datasets into resource comprising >2.8 million nuclei from prefrontal cortex across 388 individuals. For 28 cell types, assessed population-level variation in expression and chromatin families drug targets. We identified >550,000 type-specific...
The complexity and heterogeneity of schizophrenia have hindered mechanistic elucidation the development more effective therapies. Here, we performed single-cell dissection schizophrenia-associated transcriptomic changes in human prefrontal cortex across 140 individuals two independent cohorts. Excitatory neurons were most affected cell group, with transcriptional converging on neurodevelopment synapse-related molecular pathways. Transcriptional alterations included known genetic risk...
Nucleotide changes in gene regulatory elements are important determinants of neuronal development and diseases. Using massively parallel reporter assays primary human cells from mid-gestation cortex cerebral organoids, we interrogated the cis-regulatory activity 102,767 open chromatin regions, including thousands sequences with cell type-specific accessibility variants associated brain regulation. In cells, identified 46,802 active enhancer 164 that alter activity. Activity was comparable...
The molecular organization of the human neocortex historically has been studied in context its histological layers. However, emerging spatial transcriptomic technologies have enabled unbiased identification transcriptionally defined domains that move beyond classic cytoarchitecture. We used Visium gene expression platform to generate a data-driven neuroanatomical atlas across anterior-posterior axis dorsolateral prefrontal cortex. Integration with paired single-nucleus RNA-sequencing data...
Neuropsychiatric genome-wide association studies (GWASs), including those for autism spectrum disorder and schizophrenia, show strong enrichment regulatory elements in the developing brain. However, prioritizing risk genes mechanisms is challenging without a unified atlas. Across 672 diverse human brains, we identified 15,752 harboring gene, isoform, and/or splicing quantitative trait loci, mapping 3739 to cellular contexts. Gene expression heritability drops during development, likely...
Regulation of gene expression through enhancers is one the major processes shaping structure and function human brain during development. High-throughput assays have predicted thousands involved in neurodevelopment, confirming their activity orthogonal functional crucial. Here, we utilized Massively Parallel Reporter Assays (MPRAs) stem cells forebrain organoids to evaluate ~ 7000 gene-linked previously identified fetal tissues organoids. We used a Gaussian mixture model contribution...
The transcription factor DOF AFFECTING GERMINATION1 (DAG1) is a repressor of the light-mediated seed germination process. DAG1 acts downstream PHYTOCHROME INTERACTING FACTOR3-LIKE 5 (PIL5), master repressor, and negatively regulates gibberellin biosynthesis by directly repressing biosynthetic gene AtGA3ox1. Dof protein GERMINATION (DAG2) shares high degree aminoacidic identity with DAG1. While inactivation considerably increases capability seeds, dag2 mutant has seeds potential substantially...
Abstract Nucleotide changes in gene regulatory elements are important determinants of neuronal development and disease. Using massively parallel reporter assays primary human cells from mid-gestation cortex cerebral organoids, we interrogated the cis -regulatory activity 102,767 sequences, including differentially accessible cell-type specific regions developing single-nucleotide variants associated with psychiatric disorders. In cells, identified 46,802 active enhancer sequences 164...
Many psychiatric disorders exhibit sex differences, but the underlying mechanisms remain poorly understood. We analyzed transcriptomics data from 2160 postmortem adult prefrontal cortex brain samples PsychENCODE consortium in a sex-stratified study design. compared of patients with schizophrenia (SCZ), bipolar disorder (BD), and autism spectrum (ASD) control brains individuals without known history disease. found that females SCZ, BD, ASD showed higher burden transcriptomic dysfunction than...
Mutations in fused sarcoma (FUS) cause amyotrophic lateral sclerosis (ALS). FUS is a multifunctional protein involved the biogenesis and activity of several types RNAs, its role pathogenesis ALS may involve both direct effects disease-associated mutations through gain- loss-of-function mechanisms indirect due to cross talk between different classes FUS-dependent RNAs. To explore how impinge on motor neuron-specific RNA-based circuitries, we performed transcriptome profiling small long RNAs...
Deregulation of RNA metabolism has emerged as one the key events leading to degeneration motor neurons (MNs) in Amyotrophic Lateral Sclerosis (ALS) disease. Indeed, mutations on RNA-binding proteins (RBPs) or involved aspects account for majority familiar forms ALS. In particular, impact ALS-linked RBP FUS many RNA-related processes been vastly investigated. plays a pivotal role splicing regulation and its severely alter exon composition transcripts coding neurogenesis, axon guidance,...
Long non-coding RNAs (lncRNAs) are currently recognized as crucial players in nervous system development, function and pathology. In Amyotrophic Lateral Sclerosis (ALS), identification of causative mutations FUS TDP-43 or hexanucleotide repeat expansion C9ORF72 point to the essential role aberrant RNA metabolism neurodegeneration. this study, by taking advantage an vitro differentiation generating mouse motor neurons (MNs) from embryonic stem cells, we identified characterized long...
The transcription factor DOF AFFECTING GERMINATION1 (DAG1) is a repressor of seed germination acting downstream the master PHYTOCROME INTERACTING FACTOR3-LIKE 5 (PIL5). Among others, PIL5 induces expression genes encoding two DELLA proteins GA INSENSITIVE 1 (GAI) and REPRESSOR OF ga1-3 (RGA).Based on properties gai-t6 rga28 mutant seeds, we show here that absence RGA severely increases dormancy, while lack GAI only partially compensates inactivation. In addition, dag1rga28 double are...
Summary There is no clear genetic etiology or convergent pathophysiology for autism spectrum disorders (ASD). Using cortical organoids and single-cell transcriptomics, we modeled alterations in the formation of forebrain between sons with idiopathic ASD their unaffected fathers thirteen families. Alterations transcriptome suggest that pathogenesis macrocephalic normocephalic probands involves an opposite disruption balance excitatory neurons dorsal plate other lineages such as...
Abstract The transition from dividing progenitors to postmitotic motor neurons (MNs) is orchestrated by a series of events, which are mainly studied at the transcriptional level analyzing activity specific programming transcription factors. Here, we identify post‐transcriptional role MN‐specific unit (MN2) harboring lncRNA (lncMN2‐203) and two miRNAs (miR‐325‐3p miR‐384‐5p) in this transition. Through use vitro mESC differentiation single‐cell sequencing CRISPR/Cas9 mutants, demonstrate that...
Abstract Endoribonucleases participate in almost every step of eukaryotic RNA metabolism, acting either as degradative or biosynthetic enzymes. We previously identified the founding member Eukaryotic EndoU ribonuclease family, whose components display unique biochemical features and are flexibly involved important biological processes, such ribosome biogenesis, tumorigenesis viral replication. Here we report discovery CG3303 gene product, which named DendoU, a novel family Drosophila ....
Regulation of gene expression through enhancers is one the major processes shaping structure and function human brain during development. High-throughput assays have predicted thousands involved in neurodevelopment, confirming their activity orthogonal functional crucial. Here, we utilized Massively Parallel Reporter Assays (MPRAs) stem cells forebrain organoids to evaluate ~7,000 gene-linked previously identified fetal tissues organoids. We used a Gaussian mixture model contribution...
Abstract Cell differentiation involves shifts in chromatin organization allowing transcription factors (TFs) to bind enhancer elements and modulate gene expression. The TF-enhancer-gene regulatory interactions that control the formation of neuronal lineages have yet be charted humans. Here, we mapped conducted an integrative analysis epigenomic transcriptomic profiles across 60 days human forebrain organoids derived from 10 individuals with autism spectrum disorder (ASD) their neurotypical...