High spatial resolution multi-omics atlas sequencing of mouse embryos
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ABSTRACT:
PROVIDER: PRJNA574105 | ENA |
REPOSITORIES: ENA
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Project description:Microfluidic deterministic barcoding of mRNAs and proteins in tissue slides followed by high throughput sequencing enables the construction of high-spatial-resolution multi-omics atlas at the genome scale. Applying it to mouse embryo tissues revealed major tissue (sub)types in early-stage organogenesis, brain micro-vasculatures, and the fine structure of an optical vesicle at the single-cell-layer resolution.
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Project description:The mammalian brain consists of millions to billions of cells that are organized into numerous cell types with specific spatial distribution patterns and structural and functional properties. An essential step towards understanding brain function is to obtain a parts list, i.e., a catalog of cell types, of the brain. Here, we report a comprehensive and high-resolution transcriptomic and spatial cell type atlas for the whole adult mouse brain. The cell type atlas was created based on the combination of two single-cell-level, whole-brain-scale datasets: a single-cell RNA-sequencing (scRNA-seq) dataset of ~7 million cells profiled (~4.0 million cells passing quality control), and a spatially resolved transcriptomic dataset of ~4.3 million cells using MERFISH. The atlas is hierarchically organized into four nested levels of classification: 34 classes, 338 subclasses, 1,201 supertypes and 5,322 clusters. We present a newly developed online platform, Allen Brain Cell (ABC) Atlas, to visualize the mouse whole brain cell type taxonomy and atlas along with the scRNA-seq and MERFISH data and metadata sets. We systematically analyzed the neuronal, non-neuronal, and immature neuronal cell types across the brain and identified a high degree of correspondence between transcriptomic identity and spatial specificity for each cell type. The results reveal unique features of cell type organization in different brain regions, in particular, a dichotomy between the dorsal and ventral parts of the brain: the dorsal part contains relatively fewer yet highly divergent neuronal types, whereas the ventral part contains more numerous neuronal types that are more closely related to each other. We also systematically characterized cell-type specific expression of neurotransmitters, neuropeptides, and transcription factors. The study uncovered extraordinary diversity and heterogeneity in neurotransmitter and neuropeptide expression and co-expression patterns in different cell types across the brain, suggesting they mediate myriad modes of intercellular communications. Finally, we found that transcription factors are major determinants of cell type classification in the adult mouse brain and identified a combinatorial transcription factor code that defines cell types across all parts of the brain. The whole-mouse-brain transcriptomic and spatial cell type atlas establishes a benchmark reference atlas and a foundational resource for deep and integrative investigations of cellular and circuit function, development, and evolution of the mammalian brain.
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Project description:In the skin, tissue injury results in fibrosis in the form of scars composed of dense extracellular matrix deposited by fibroblasts. The therapeutic goal of regenerative wound healing has remained elusive in part because principles of fibroblast programming and adaptive response to injury remain incompletely understood. Here, we present a multimodal -omics platform for the comprehensive study of cell populations in complex tissue, which has allowed us to characterize the cells involved in wound healing across both time and space. We employ a stented wound model that recapitulates human tissue repair kinetics and multiple Rainbow transgenic lines to precisely track fibroblast fate during the physiologic response to injury. Through integrated analysis of single cell chromatin landscapes and gene expression states, coupled with spatial transcriptomic profiling, we are able to impute fibroblast epigenomes with temporospatial resolution. This has allowed us to define the mechanisms controlling cell fate during migration, proliferation, and differentiation following tissue injury and thereby reexamine the canonical phases of wound healing. We show that wounding triggers a polyclonal proliferation of tissue-resident, mechano-responsive fibroblasts, the subpopulations of which inhabit spatially-distinct regions within the wound and harbor distinct activities. These findings have broad implications for the study of tissue repair in complex organ systems.
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