Whole-brain annotation and multi-connectome cell typing of Drosophila

Nature, Journal Year: 2024, Volume and Issue: 634(8032), P. 139 - 152

Published: Oct. 2, 2024

Language: Английский

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Whole-brain annotation and multi-connectome cell typing quantifies circuit stereotypy inDrosophila

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: June 27, 2023

Abstract The fruit fly Drosophila melanogaster combines surprisingly sophisticated behaviour with a highly tractable nervous system. A large part of the fly’s success as model organism in modern neuroscience stems from concentration collaboratively generated molecular genetic and digital resources. As presented our FlyWire companion paper 1 , this now includes first full brain connectome an adult animal. Here we report systematic hierarchical annotation ∼130,000-neuron including neuronal classes, cell types developmental units (hemilineages). This enables any researcher to navigate huge dataset find systems neurons interest, linked literature through Virtual Fly Brain database 2 . Crucially, resource 4,552 types. 3,094 are rigorous consensus validations previously proposed “hemibrain” 3 In addition, propose 1,458 new types, arising mostly fact that spans whole brain, whereas hemibrain derives subvolume. Comparison showed type counts strong connections were largely stable, but connection weights variable within across animals. Further analysis defined simple heuristics for interpretation: stronger than 10 unitary synapses or providing >1% input target conserved. Some increased variability connectomes: most common mushroom body, required learning memory, is almost twice numerous hemibrain. We evidence functional homeostasis adjustments absolute amount excitatory while maintaining excitation-inhibition ratio. Finally, surprisingly, about one third could not yet be reliably identified connectome. therefore suggest should robust inter-individual variation, namely groups cells quantitatively more similar different other same brain. Joint connectomes demonstrates viability utility definition. Our work defines atlas provides both intellectual framework open source toolchain brain-scale comparative connectomics.

Language: Английский

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Spatial multi-omics: novel tools to study the complexity of cardiovascular diseases

Genome Medicine, Journal Year: 2024, Volume and Issue: 16(1)

Published: Jan. 18, 2024

Abstract Spatial multi-omic studies have emerged as a promising approach to comprehensively analyze cells in tissues, enabling the joint analysis of multiple data modalities like transcriptome, epigenome, proteome, and metabolome parallel or even same tissue section. This review focuses on recent advancements spatial multi-omics technologies, including novel computational approaches. We discuss low-resolution high-resolution methods which can resolve up 10,000 individual molecules at subcellular level. By applying integrating these techniques, researchers recently gained valuable insights into molecular circuits mechanisms govern cell biology along cardiovascular disease spectrum. provide an overview current approaches, with focus integration datasets, highlighting strengths weaknesses various pipelines. These tools play crucial role analyzing interpreting facilitating discovery new findings, enhancing translational research. Despite nontrivial challenges, such need for standardization experimental setups, analysis, improved tools, application holds tremendous potential revolutionizing our understanding human processes identification biomarkers therapeutic targets. Exciting opportunities lie ahead field will likely contribute advancement personalized medicine diseases.

Language: Английский

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Integrated multimodal cell atlas of Alzheimer’s disease

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: May 23, 2023

Alzheimer's disease (AD) is the most common cause of dementia in older adults. Neuropathological and imaging studies have demonstrated a progressive stereotyped accumulation protein aggregates, but underlying molecular cellular mechanisms driving AD progression vulnerable cell populations affected by remain coarsely understood. The current study harnesses single spatial genomics tools knowledge from BRAIN Initiative Cell Census Network to understand impact on middle temporal gyrus types. We used image-based quantitative neuropathology place 84 donors spanning spectrum pathology along continuous pseudoprogression score multiomic technologies profile nuclei each donor, mapping their transcriptomes, epigenomes, coordinates type reference with unprecedented resolution. Temporal analysis cell-type proportions indicated an early reduction Somatostatin-expressing neuronal subtypes late decrease supragranular intratelencephalic-projecting excitatory Parvalbumin-expressing neurons, increases disease-associated microglial astrocytic states. found complex gene expression differences, ranging global type-specific effects. These effects showed different patterns indicating diverse perturbations as function progression. A subset particularly severe phenotype, which correlated steeper cognitive decline. created freely available public resource explore these data accelerate progress research at SEA-AD.org.

Language: Английский

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A guide to the BRAIN Initiative Cell Census Network data ecosystem

PLoS Biology, Journal Year: 2023, Volume and Issue: 21(6), P. e3002133 - e3002133

Published: June 30, 2023

Characterizing cellular diversity at different levels of biological organization and across data modalities is a prerequisite to understanding the function cell types in brain. Classification neurons also essential manipulate controlled ways understand their variation vulnerability brain disorders. The BRAIN Initiative Cell Census Network (BICCN) an integrated network data-generating centers, archives, standards developers, with goal systematic multimodal type profiling characterization. Emphasis BICCN on whole mouse demonstration prototype feasibility for human nonhuman primate (NHP) brains. Here, we provide guide spatial approaches employed by BICCN, accessing using these extensive resources, including Data Center (BCDC), which serves manage integrate ecosystem. We illustrate power ecosystem through vignettes highlighting several analysis visualization tools. Finally, present emerging that have been developed or adopted toward Findable, Accessible, Interoperable, Reusable (FAIR) neuroscience. combined provides comprehensive resource exploration

Language: Английский

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Integrated multimodal cell atlas of Alzheimer’s disease

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: May 9, 2023

Abstract Alzheimer’s disease (AD) is the most common cause of dementia in older adults. Neuropathological and imaging studies have demonstrated a progressive stereotyped accumulation protein aggregates, but underlying molecular cellular mechanisms driving AD progression vulnerable cell populations affected by remain coarsely understood. The current study harnesses single spatial genomics tools knowledge from BRAIN Initiative Cell Census Network to understand impact on middle temporal gyrus types. We used image-based quantitative neuropathology place 84 donors spanning spectrum pathology along continuous pseudoprogression score multiomic technologies profile nuclei each donor, mapping their transcriptomes, epigenomes, coordinates type reference with unprecedented resolution. Temporal analysis cell-type proportions indicated an early reduction Somatostatin-expressing neuronal subtypes late decrease supragranular intratelencephalic-projecting excitatory Parvalbumin-expressing neurons, increases disease-associated microglial astrocytic states. found complex gene expression differences, ranging global type-specific effects. These effects showed different patterns indicating diverse perturbations as function progression. A subset particularly severe phenotype, which correlated steeper cognitive decline. created freely available public resource explore these data accelerate progress research at SEA-AD.org .

Language: Английский

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Evolution of gene expression across brain regions in behaviourally divergent deer mice

Molecular Ecology, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 23, 2024

Abstract The evolution of innate behaviours is ultimately due to genetic variation likely acting in the nervous system. Gene regulation may be particularly important because it can evolve a modular brain‐region specific fashion through concerted action cis ‐ and trans ‐regulatory changes. Here, investigate transcriptional its regulatory basis across brain, we perform RNA sequencing (RNA‐Seq) on ten brain subregions two sister species deer mice ( Peromyscus maniculatus P. polionotus )—which differ range behaviours, including their social system—and F 1 hybrids. We find that most gene expression distinguishes subregions, followed by species. Interspecific differential (DE) pervasive (52–59% expressed genes), whereas number DE genes between sexes modest overall (~3%). Interestingly, identity varies considerably regions. Much this modularity divergence, while 43% were consistently assigned same class (e.g. conserved, or divergence), similar more different classes. Together, these results highlight differences divergence which key explain how contribute astonishing diversity animal behaviours.

Language: Английский

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Nicheformer: a foundation model for single-cell and spatial omics

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 17, 2024

Tissue makeup relies fundamentally on the cellular microenvironment. Spatial single-cell genomics allows probing underlying interactions in an unbiased, scalable fashion. To learn a unified cell representation that accounts for local dependencies microenvironment, we propose Nicheformer, transformer-based foundation model combines human and mouse dissociated targeted spatial transcriptomics data. Pretrained over 57 million 53 spatially resolved cells across 73 tissues reconstruction, is fine-tuned tasks omics data to decode information. Nicheformer excels linear-probing fine-tuning scenarios novel set of downstream tasks, particular composition prediction label prediction. We further show existing models trained alone are not capable recapitulating complexity their microenvironments, indicating multiscale required understand complex at scale. enables context cells, allowing transfer rich information scRNA-seq datasets. Overall, sets stage next generation machine-learning analysis.

Language: Английский

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Developmental Mouse Brain Common Coordinate Framework

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 15, 2023

3D standard reference brains serve as key resources to understand the spatial organization of brain and promote interoperability across different studies. However, unlike adult mouse brain, lack atlases for developing has hindered advancement our understanding development. Here, we present a multimodal developmental common coordinate framework (DevCCF) spanning embryonic day (E) 11.5, E13.5, E15.5, E18.5, postnatal (P) 4, P14, P56 with anatomical segmentations defined by ontology. At each age, DevCCF features undistorted morphologically averaged atlas templates created from Magnetic Resonance Imaging co-registered high-resolution light sheet fluorescence microscopy. Expert-curated at age adhere an updated prosomeric model can be explored via interactive web-visualizer. As use case, employed unveil emergence GABAergic neurons in brains. Moreover, integrated Allen CCFv3 into template stereotaxic coordinates mapped transcriptome cell-type data In summary, is openly accessible resource that used large-scale integration gain comprehensive

Language: Английский

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Single-cell DNA Methylome and 3D Multi-omic Atlas of the Adult Mouse Brain

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: April 18, 2023

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

Language: Английский

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