Molecular atlas of the adult mouse brain

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

doi:10.1126/sciadv.abb3446

Cited by 222 publications

(197 citation statements)

References 54 publications

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“…In contrast, ST preserves the spatial information of gene expression in their true tissue context, thus categorically complementing single cell transcriptomic approaches. The emerging possibilities of combining spatial transcriptomic data with de-novo and existing single cell and other omics data of the same tissue offer unprecedented levels of insight into the biology of the tissue 38,48 .…”

Section: Discussionmentioning

confidence: 99%

Spatial Transcriptomics to define transcriptional patterns of zonation and structural components in the liver

Hildebrandt

Andersson

Saarenpää

et al. 2021

Preprint

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Reconstruction of heterogeneity through single-cell transcriptional profiling has greatly advanced our understanding of the spatial liver transcriptome in recent years. However, global transcriptional differences across lobular units remain elusive in physical space. Here, we implement Spatial Transcriptomics to perform transcriptomic analysis across sectioned liver tissue. We confirm that the heterogeneity in this complex tissue is predominantly determined by lobular zonation. By introducing novel computational approaches, we enable transcriptional gradient measurements between tissue structures, including several lobules in a variety of orientations. Further, our data suggests the presence of previously transcriptionally uncharacterized structures within liver tissue, contributing to the overall spatial heterogeneity of the organ. This study demonstrates how comprehensive spatial transcriptomic technologies can be used to delineate extensive spatial gene expression patterns in the liver, indicating its future impact for studies of liver function, development and regeneration as well as its potential in pre-clinical and clinical pathology.

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Section: Discussionmentioning

confidence: 99%

Spatial Transcriptomics to define transcriptional patterns of zonation and structural components in the liver

Hildebrandt

Andersson

Saarenpää

et al. 2021

Preprint

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“…The findings above suggested that the local heterogeneity of drug efficacy may be controlled by intrinsic properties of the host brain, some of which may be genetically specified. We therefore compared the plaque-size SAVs of NB360 and LIN5044 to a gene-expression atlas reporting whole-genome expression at >30’000 spots of the mouse brain 30 . We calculated the mutual information (MI) as a similarity metric describing the interdependence of two random variables.…”

Section: Resultsmentioning

confidence: 99%

Longitudinal quantitative whole-brain microscopy reveals distinct temporal and spatial efficacies of anti-Aβ therapies

Kirschenbaum

Voigt

Dadgar‐Kiani

et al. 2021

Preprint

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Genetic and biochemical evidence suggests a role for amyloid-β (Aβ) in Alzheimer’s disease, yet many anti-Aβ treatments are clinically ineffective. Regional heterogeneity of efficacy may contribute to these disappointing results. Here we compared the regiospecificity of various anti-Aβ treatments by combining focused electrophoretic whole-brain clearing, amyloid labelling and light-sheet imaging with whole-brain analyses of plaque topology in Aβ-overexpressing mice. Aβ plaque numbers progressed from around 1’200’000 to 2’500’000 over a 9-month period. We then assessed the regiospecific plaque clearance in mice subjected to β-secretase inhibition, amyloid intercalation by polythiophenes, and anti-Aβ antibodies. Each treatment showed unique spatiotemporal Aβ clearance signatures, with polythiophenes emerging as potent anti-Aβ compounds with promising pharmacokinetic properties and the anti-Aβ antibody showing only minor effects. By aligning (25 µm)3 voxels that showed drug effectiveness to spatial transcriptomics atlases, we identified genes matching regiospecific Aβ clearance. As expected, Bace1 expression was highly correlated with the regiospecific efficacy of BACE inhibition. In addition, we found that voxels cleared by polythiophenes correlated with transcripts encoding synaptic proteins, whereas voxels cleared by BACE inhibition correlated with oligodendrocyte-specific genes. The differential regional susceptibility of distinct plaque populations to specific treatments may explain the clinical failure of anti-Aβ therapies, and suggests that combinatorial regimens may improve functional outcomes.

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“…High throughput transcriptomics and proteomics of developing CPNs and CC tissue identified hundreds more possible molecular players that require further verification and functional characterization. Whole-brain spatial transcriptomics revealed new area- and layer-specific subregions within the adult mouse cerebral cortex [ 139 ]. Cross-referencing these new findings with previous gene expression data would further validate and expand current understanding of CPN identities.…”

Section: Discussionmentioning

confidence: 99%

New Molecular Players in the Development of Callosal Projections

Torii

2020

Cells

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Cortical development in humans is a long and ongoing process that continuously modifies the neural circuitry into adolescence. This is well represented by the dynamic maturation of the corpus callosum, the largest white matter tract in the brain. Callosal projection neurons whose long-range axons form the main component of the corpus callosum are evolved relatively recently with a substantial, disproportionate increase in numbers in humans. Though the anatomy of the corpus callosum and cellular processes in its development have been intensively studied by experts in a variety of fields over several decades, the whole picture of its development, in particular, the molecular controls over the development of callosal projections, still has many missing pieces. This review highlights the most recent progress on the understanding of corpus callosum formation with a special emphasis on the novel molecular players in the development of axonal projections in the corpus callosum.

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Molecular atlas of the adult mouse brain

Cited by 222 publications

References 54 publications

Spatial Transcriptomics to define transcriptional patterns of zonation and structural components in the liver

Spatial Transcriptomics to define transcriptional patterns of zonation and structural components in the liver

Longitudinal quantitative whole-brain microscopy reveals distinct temporal and spatial efficacies of anti-Aβ therapies

New Molecular Players in the Development of Callosal Projections

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