Molecular Atlas of the Adult Mouse Brain

Ortiz, Cantin; Navarro, José Fernández; Jurek, Aleksandra; Märtin, Antje; Lundeberg, Joakim; Meletis, Konstantinos

doi:10.1101/784181

Cited by 60 publications

(92 citation statements)

References 38 publications

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“…S1). Consistent with previous studies 4,25 , STANN showed an abundance of olfactory ensheathing cells in FOVs originating from the GL (Fig. 3B).…”

Section: Bulbsupporting

confidence: 92%

“…A mechanistic understanding of a tissue depends on its cell-types and their transcriptional properties, spatial organization, and communication 1 . Methodological advances to address these mechanistic details are essential for the study of development, physiology, and disease [2][3][4][5][6][7][8] . Spatial transcriptomics (ST) and single-cell RNA-seq (scRNA-seq) are complementary technologies, each with its own strengths and weaknesses, for studying complex tissues at a single-cell resolution 2 .…”

Section: Introductionmentioning

confidence: 99%

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Integrative Analysis of Spatial and Single-Cell Transcriptomics Reveals Principles of Tissue Organization and Intercellular Communication in Mouse Olfactory Bulb

Canozo

Zuo

Martin

et al. 2020

Preprint

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Intercellular communication and spatial organization of cells are two critical aspects of a tissue’s function. Understanding these aspects requires integrating data from single-cell RNA-Seq (scRNA-seq) and spatial transcriptomics (ST), the two cutting edge technologies that offer complementary insights into tissue composition, architecture, and function. Integrating these data types is non-trivial since they differ widely in the number of profiled genes and often do not share marker genes for given cell-types. We developed STANN, a neural network model that overcomes these methodological challenges. Given ST and scRNA-seq data of a tissue, STANN models cell-types in the scRNA-seq dataset from the genes that are profiled by both ST and scRNA-seq. The trained STANN model then assigns cell-types to the ST dataset. We apply STANN to assign cell-types in a recent ST dataset (SeqFISH+) of mouse olfactory bulb (MOB). Our analysis of STANN’s assigned cell-types revealed principles of tissue architecture and intercellular communication at unprecedented detail. We find that cell-type compositions are disproportionate in the tissue, yet their relative proportions are spatially consistent within individual morphological layers. Surprisingly, within a morphological layer, there is a high spatial variation in cell-type colocalization patterns and intercellular communication mechanisms. Our analysis suggests that spatially localized gene regulatory networks may account for such variability in intercellular communication mechanisms.

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“…S1). Consistent with previous studies 4,25 , STANN showed an abundance of olfactory ensheathing cells in FOVs originating from the GL (Fig. 3B).…”

Section: Bulbsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Integrative Analysis of Spatial and Single-Cell Transcriptomics Reveals Principles of Tissue Organization and Intercellular Communication in Mouse Olfactory Bulb

Canozo

Zuo

Martin

et al. 2020

Preprint

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“…dSPNs from discrete spatial domains project to the GPe The dStr is divided into molecularly, synaptically, and functionally distinct subregions (Smith et al, 2004;Palmiter, 2009, 2010;Nambu, 2011;Hintiryan et al, 2016;Hooks et al, 2018;Poulin et al, 2018;Martin et al, 2019;Alegre-Cortés et al, 2020;Ortiz et al, 2020). The dorsomedial striatum (DMS) and dorsolateral striatum (DLS) are thought to be involved in regulating goal-directed and habitual behavior, respectively (Yin and Knowlton, 2006;Balleine and O'Doherty, 2010;Redgrave et al, 2010;Cox and Witten, 2019).…”

Section: Results (3846 Words) Dspns Send Terminating Axons To the Gpementioning

confidence: 99%

Striatal Direct Pathway Targets Npas1⁺Pallidal Neurons

Cui¹,

Chang³

et al. 2020

Preprint

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The classic basal ganglia circuit model asserts a complete segregation of the two striatal output pathways. Empirical data argue that, in addition to indirect-pathway striatal projection neurons (iSPNs), direct-pathway striatal projection neurons (dSPNs) innervate the external globus pallidus (GPe). However, the functions of the latter were not known. In this study, we interrogated the organization principles of striatopallidal projections and how they are involved in full-body movement in mice (both males and females). In contrast to the canonical motor-promoting role of dSPNs in the dorsomedial striatum (DMSdSPNs), optogenetic stimulation of dSPNs in the dorsolateral striatum (DLSdSPNs) suppressed locomotion. Circuit analyses revealed that dSPNs selectively target Npas1+ neurons in the GPe. In a chronic 6-hydroxydopamine lesion model of Parkinson’s disease, the dSPN-Npas1+ projection was dramatically strengthened. As DLSdSPN-Npas1+ projection suppresses movement, the enhancement of this projection represents a circuit mechanism for the hypokinetic symptoms of Parkinson’s disease that has not been previously considered.Significance statementIn the classic basal ganglia model, the striatum is described as a divergent structure—it controls motor and adaptive functions through two segregated, opponent output streams. However, the experimental results that show the projection from direct-pathway neurons to the external pallidum have been largely ignored. Here, we showed that this striatopallidal sub-pathway targets a select subset of neurons in the external pallidum and is motor-suppressing. We found that this sub-pathway undergoes plastic changes in a Parkinson’s disease model. In particular, our results suggest that the increase in strength of this sub-pathway contributes to the slowness or reduced movements observed in Parkinson’s disease.

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“…Such spatial transcriptomics techniques can be correlated and complemented with single-cell transcriptomics Phillips et al, 2019;Qian et al, 2020), and recent developments using viral barcoding have also enabled the integration of long-range projection information in a brain-wide manner (Chen et al, 2019). However, these approaches only retrieve multimodal information for small subsets of cells and/or their scalability is not straight-forward beyond a set of tissue slices (Ortiz et al, 2019), though this could suffice for small organisms (Ebbing et al, 2018).…”

Section: Seeking Multimodalitymentioning

confidence: 99%

Whole-body integration of gene expression and single-cell morphology

Vergara

Pape

Meechan

et al. 2020

Preprint

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Animal bodies are composed of hundreds of cell types that differ in location, morphology, cytoarchitecture, and physiology. This is reflected by cell type-specific transcription factors and downstream effector genes implementing functional specialisation. Here, we establish and explore the link between cell type-specific gene expression and subcellular morphology for the entire body of the marine annelid Platynereis dumerilii. For this, we registered a whole-body cellular expression atlas to a high-resolution electron microscopy dataset, automatically segmented all cell somata and nuclei, and clustered the cells according to gene expression or morphological parameters. We show that collective gene expression most efficiently identifies spatially coherent groups of cells that match anatomical boundaries, which indicates that combinations of regionally expressed transcription factors specify tissue identity. We provide an integrated browser as a Fiji plugin to readily explore, analyse and visualise multimodal datasets with remote ondemand access to all available datasets. Figure 1: Ultrastructure of a whole Platynereis by serial block-face scanning electron microscopy.A: The 3D SBEM dataset can be observed in multiple orientations, either along the acquisition plane (transversal plane, top row) or as orthogonal projections (horizontal plane, bottom row; scale bar: 50 µm). B-E: fine ultrastructure is revealed when exploring the datasets at native resolution (10 nm pixel-size x/y; scale bars: 2 µm). B: epithelial cell, interfacing the cuticle and the underlying muscle. Bundles of cytoskeletal filaments (arrowhead) form part of the attachment complex (inset). C: the adult eye forms a pigment cup composed of pigment cells (PiC) and rhabdomeric photoreceptors (rPRC). The photoreceptors extend a distal segment made by microvillar projections (mi) for light detection. In the centre of the pigment cup is the vitreous body (vb). D: longitudinal muscle fibres are cut transversally displaying cross-sections of the sarcomere as well as of the sarcoplasmic reticulum that contacts the plasma membrane (inset). E: cross section of the distal part of the nephridia, highlighting the autocell junction (arrow) which forms a lumen. The lumen houses a bundle of motile cilia (identified by the 9+2 microtubule arrangement, inset), which are contributed by each cell of the nephridium, noted by the presence of basal bodies. Panels B to E are snapshots selected from the full volume and can be retrieved directly from the PlatyBrowser "Bookmark" function. Supplementary Figure 2A). Figure 2 gives a few examples of the achieved segmentation quality for epidermal cells (B), muscles (C) and nephridia (D). We measured nuclei sizes to range from 33.6 to 147.5 cubic microns, and cell sizes from 59.8 to 1224.6 cubic microns. Note that neurites in the neuropil have not been segmented, as they are not sufficiently preserved in the EM volume for automated segmentation. Figure 2: Segmentation of nuclei, cells, tissues and body parts.A. Cells and nuclei ar...

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Molecular Atlas of the Adult Mouse Brain

Cited by 60 publications

References 38 publications

Integrative Analysis of Spatial and Single-Cell Transcriptomics Reveals Principles of Tissue Organization and Intercellular Communication in Mouse Olfactory Bulb

Integrative Analysis of Spatial and Single-Cell Transcriptomics Reveals Principles of Tissue Organization and Intercellular Communication in Mouse Olfactory Bulb

Striatal Direct Pathway Targets Npas1⁺Pallidal Neurons

Whole-body integration of gene expression and single-cell morphology

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Molecular Atlas of the Adult Mouse Brain

Cited by 60 publications

References 38 publications

Integrative Analysis of Spatial and Single-Cell Transcriptomics Reveals Principles of Tissue Organization and Intercellular Communication in Mouse Olfactory Bulb

Integrative Analysis of Spatial and Single-Cell Transcriptomics Reveals Principles of Tissue Organization and Intercellular Communication in Mouse Olfactory Bulb

Striatal Direct Pathway Targets Npas1+Pallidal Neurons

Whole-body integration of gene expression and single-cell morphology

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Striatal Direct Pathway Targets Npas1⁺Pallidal Neurons