A5012454695- Single-cell and spatial transcriptomics
- Neurobiology and Insect Physiology Research
- Genomics and Chromatin Dynamics
- CRISPR and Genetic Engineering
- Retinal Development and Disorders
- Olfactory and Sensory Function Studies
- Fossil Insects in Amber
- Amyotrophic Lateral Sclerosis Research
- RNA Research and Splicing
- Pluripotent Stem Cells Research
- Insect and Arachnid Ecology and Behavior
- Neuroinflammation and Neurodegeneration Mechanisms
- MicroRNA in disease regulation
- Sleep and Wakefulness Research
- 3D Printing in Biomedical Research
- Parkinson's Disease Mechanisms and Treatments
- RNA regulation and disease
- Neurogenesis and neuroplasticity mechanisms
- Circadian rhythm and melatonin
- Cellular Mechanics and Interactions
- Autophagy in Disease and Therapy
- Mitochondrial Function and Pathology
- Invertebrate Immune Response Mechanisms
- Adenosine and Purinergic Signaling
- Gene Regulatory Network Analysis
VIB-KU Leuven Center for Brain & Disease Research
2017-2025
KU Leuven
2014-2025
Allen Institute for Brain Science
2024-2025
VIB-KU Leuven Center for Cancer Biology
2024-2025
The diversity of cell types and regulatory states in the brain, how these change during aging, remains largely unknown. We present a single-cell transcriptome atlas entire adult Drosophila melanogaster brain sampled across its lifespan. Cell clustering identified 87 initial clusters that are further subclustered validated by targeted cell-sorting. Our data show high granularity identify wide range types. Gene network analyses using SCENIC revealed heterogeneity linked to energy consumption....
For more than 100 years, the fruit fly
How neural circuits develop in the human brain has remained almost impossible to study at neuronal level. Here, we investigate cortical neuron development, plasticity, and function using a mouse/human chimera model which xenotransplanted pyramidal neurons integrate as single cells into mouse cortex. Combined tracing, electrophysiology, vivo structural functional imaging of transplanted reveal coordinated developmental roadmap recapitulating key milestones development. The display prolonged...
Neuronal development in the human cerebral cortex is considerably prolonged compared with that of other mammals. We explored whether mitochondria influence species-specific timing cortical neuron maturation. By comparing and mouse neuronal maturation at high temporal cell resolution, we found a slower neurons mouse, together lower metabolic activity, particularly oxidative phosphorylation. Stimulation metabolism resulted accelerated vitro vivo, leading to cells weeks ahead time, whereas its...
Combinations of transcription factors govern the identity cell types, which is reflected by genomic enhancer codes. We used deep learning to characterize these codes and devised three metrics compare types in telencephalon across amniotes. To this end, we generated single-cell multiome spatially resolved transcriptomics data chicken telencephalon. Enhancer orthologous nonneuronal γ-aminobutyric acid–mediated (GABAergic) show a high degree similarity amniotes, whereas excitatory neurons...
Genomic enhancers regulate spatio-temporal gene expression by recruiting specific combinations of transcription factors (TFs). When TFs are bound to active regulatory regions, they displace canonical nucleosomes, making these regions biochemically detectable as nucleosome-depleted or accessible/open chromatin. Here we ask whether open chromatin profiling can be used identify the entire repertoire promoters and underlying tissue-specific during normal development oncogenesis in vivo. To this...
Abstract The evolution of winged insects revolutionized terrestrial ecosystems and led to the largest animal radiation on Earth. However, we still have an incomplete picture genomic changes that underlay this diversification. Mayflies, as one sister groups all other insects, are key understanding radiation. Here, describe genome mayfly Cloeon dipterum its gene expression throughout aquatic aerial life cycle specific organs. We discover expansion odorant-binding-protein genes, some expressed...
Single-cell technologies allow measuring chromatin accessibility and gene expression in each cell, but jointly utilizing both layers to map bona fide regulatory networks enhancers remains challenging. Here, we generate independent single-cell RNA-seq ATAC-seq atlases of the Drosophila eye-antennal disc spatially integrate data into a virtual latent space that mimics organization 2D tissue using ScoMAP (Single-Cell Omics Mapping spatial Axes Pseudotime ordering). To validate predicted...
Tissues achieve their complex spatial organization through an interplay between gene regulatory networks, cell-cell communication, and physical interactions mediated by mechanical forces. Current strategies to generate in-vitro tissues have largely failed implement such active, dynamically coordinated manipulations, relying instead on extracellular matrices which respond to, rather than impose Here, we develop devices that enable the actuation of organoids. We show active forces increase...
Abstract The ability to obtain single cell transcriptomes for stable types and dynamic states is ushering in a new era biology. We created the Tabula Drosophilae , atlas of adult fruit fly which includes 580k cells from 15 individually dissected sexed tissues as well entire head body. Over 100 researchers community contributed annotations >250 distinct across all tissues. provide an in-depth analysis type-related gene signatures transcription factor markers, sexual dimorphism, whole...
Abstract Early Alzheimer’s disease (AD) is associated with hippocampal hyperactivity and decreased sleep quality. Here we show that homeostatic mechanisms transiently counteract the increased excitatory drive to CA1 neurons in App NL-G-F mice, but this mechanism fails older mice. Spatial transcriptomics analysis identifies Pmch as part of adaptive response encodes melanin-concentrating hormone (MCH), which produced sleep–active lateral hypothalamic project modulate memory. We MCH...
The sleep-wake cycle is determined by circadian and sleep homeostatic processes. However, the molecular impact of these processes their interaction in different brain cell populations are unknown. To fill this gap, we profiled single-cell transcriptome adult Drosophila brains across four times. We show type-specific transcriptomic changes, with glia displaying largest variation. Glia also among few types whose gene expression correlates both homeostat clock. drive level affect clock...
Spatial transcriptomics workflows using barcoded capture arrays are commonly used for resolving gene expression in tissues. However, existing techniques either limited by array density or cost prohibitive large-scale atlasing. We present Nova-ST, a dense nano-patterned spatial technique derived from randomly Illumina sequencing flow cells. Nova-ST enables customized, low-cost, flexible, and high-resolution profiling of large tissue sections. Benchmarking on mouse brain sections demonstrates...
Parkinson’s disease (PD) is commonly associated with the loss of dopaminergic neurons in substantia nigra , but many other cell types are affected even before neuron occurs. Recent studies have linked oligodendrocytes to early stages PD, though their precise role still unclear. Pink1 mutated familial PD and through unbiased single-cell sequencing entire brain Drosophila models, we observed significant gene deregulation ensheathing glia (EG); cells that share functional similarities...
Transcription factors regulate their target genes by binding to regulatory regions in the genome. Although preferences of TP53 are known, it remains unclear what distinguishes functional enhancers from nonfunctional binding. In addition, genome is scattered with recognition sequences that remain unoccupied. Using two complementary techniques multiplex enhancer-reporter assays, we discovered could be discriminated events occurrence a single canonical motif. By combining machine learning...
are validated by ChIP-seq and correlate with chromatin opening
microRNA-132 (miR-132), a known neuronal regulator, is one of the most robustly downregulated microRNAs (miRNAs) in brain Alzheimer's disease (AD) patients. Increasing miR-132 AD mouse ameliorates amyloid and Tau pathologies, also restores adult hippocampal neurogenesis memory deficits. However, functional pleiotropy miRNAs requires in-depth analysis effects supplementation before it can be moved forward for therapy. We employ here loss- gain-of-function approaches using single-cell...
Abstract Spatial transcriptomics workflows using barcoded capture arrays are commonly used for resolving gene expression in tissues. However, existing techniques either limited by array density or cost prohibitive large scale atlasing. We present Nova-ST, a dense nano-patterned spatial technique derived from randomly Illumina sequencing flow cells. Nova-ST enables customized, low cost, flexible, and high-resolution profiling of tissue sections. Benchmarking on mouse brain sections...
The existence and functional significance of immature neurons in the adult human brain, particularly context neurodegenerative disorders, remain controversial. While rodent studies have highlighted active roles for adult-born hippocampus under both healthy conditions Alzheimer's disease (AD), evidence from brain is limited lacks detailed molecular characterization. To address this gap, we performed single-nucleus RNA sequencing aged healthy, AD dementia-resilient to probe neuronal signatures...
Parkinson’s disease (PD) is commonly associated with the loss of dopaminergic neurons in substantia nigra , but many other cell types are affected even before neuron occurs. Recent studies have linked oligodendrocytes to early stages PD, though their precise role still unclear. Pink1 mutated familial PD and through unbiased single-cell sequencing entire brain Drosophila models, we observed significant gene deregulation ensheathing glia (EG); cells that share functional similarities...