Museum of spatial transcriptomics

Nature Methods, Journal Year: 2022, Volume and Issue: 19(5), P. 534 - 546

Published: March 10, 2022

Language: Английский

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Phenotypic variation of transcriptomic cell types in mouse motor cortex

Nature, Journal Year: 2020, Volume and Issue: 598(7879), P. 144 - 150

Published: Nov. 12, 2020

Abstract Cortical neurons exhibit extreme diversity in gene expression as well morphological and electrophysiological properties 1,2 . Most existing neural taxonomies are based on either transcriptomic 3,4 or morpho-electric 5,6 criteria, it has been technically challenging to study both aspects of neuronal the same set cells 7 Here we used Patch-seq 8 combine patch-clamp recording, biocytin staining, single-cell RNA sequencing more than 1,300 adult mouse primary motor cortex, providing a annotation almost all transcriptomically defined cell types. We found that, although broad families types (those expressing Vip , Pvalb Sst so on) had distinct essentially non-overlapping phenotypes, individual within family were not separated space. Instead, there was continuum variability morphology electrophysiology, with neighbouring showing similar features, often without clear boundaries between them. Our results suggest that neocortex do always form discrete entities. hierarchy consists branches at level families, but can continuous correlated morpho-electrical landscapes families.

Language: Английский

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Morphological diversity of single neurons in molecularly defined cell types

Nature, Journal Year: 2021, Volume and Issue: 598(7879), P. 174 - 181

Published: Oct. 6, 2021

Abstract Dendritic and axonal morphology reflects the input output of neurons is a defining feature neuronal types 1,2 , yet our knowledge its diversity remains limited. Here, to systematically examine complete single-neuron morphologies on brain-wide scale, we established pipeline encompassing sparse labelling, whole-brain imaging, reconstruction, registration analysis. We fully reconstructed 1,741 from cortex, claustrum, thalamus, striatum other brain regions in mice. identified 11 major projection neuron with distinct morphological features corresponding transcriptomic identities. Extensive projectional was found within each these types, basis which some were clustered into more refined subtypes. This follows set generalizable principles that govern long-range projections at different levels, including molecular correspondence, divergent or convergent projection, axon termination pattern, regional specificity, topography, individual cell variability. Although clear concordance profiles evident level type, fine-grained often does not readily correlate subtypes derived unsupervised clustering, highlighting need for single-cell cross-modality studies. Overall, study demonstrates crucial quantitative description anatomy cell-type classification, as reveals plethora ways their members may contribute configuration function respective circuits.

Language: Английский

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What is a cell type and how to define it?

Cell, Journal Year: 2022, Volume and Issue: 185(15), P. 2739 - 2755

Published: July 1, 2022

Language: Английский

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The emerging landscape of spatial profiling technologies

Nature Reviews Genetics, Journal Year: 2022, Volume and Issue: 23(12), P. 741 - 759

Published: July 20, 2022

Language: Английский

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The expanding vistas of spatial transcriptomics

Nature Biotechnology, Journal Year: 2022, Volume and Issue: 41(6), P. 773 - 782

Published: Oct. 3, 2022

Language: Английский

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A transcriptomic and epigenomic cell atlas of the mouse primary motor cortex

Nature, Journal Year: 2021, Volume and Issue: 598(7879), P. 103 - 110

Published: Oct. 6, 2021

Abstract Single-cell transcriptomics can provide quantitative molecular signatures for large, unbiased samples of the diverse cell types in brain 1–3 . With proliferation multi-omics datasets, a major challenge is to validate and integrate results into biological understanding cell-type organization. Here we generated transcriptomes epigenomes from more than 500,000 individual cells mouse primary motor cortex, structure that has an evolutionarily conserved role locomotion. We developed computational statistical methods multimodal data quantitatively reproducibility. The resulting reference atlas—containing over 56 neuronal are highly replicable across analysis methods, sequencing technologies modalities—is comprehensive genomic account non-neuronal cortex. atlas includes population excitatory neurons resemble pyramidal layer 4 other cortical regions further discovered thousands concordant marker genes gene regulatory elements these types. Our highlight complex regulation will directly enable design reagents target specific cortex functional analysis.

Language: Английский

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The dawn of spatial omics

Science, Journal Year: 2023, Volume and Issue: 381(6657)

Published: Aug. 3, 2023

Spatial omics has been widely heralded as the new frontier in life sciences. This term encompasses a wide range of techniques that promise to transform many areas biology and eventually revolutionize pathology by measuring physical tissue structure molecular characteristics at same time. Although field came age past 5 years, it still suffers from some growing pains: barriers entry, robustness, unclear best practices for experimental design analysis, lack standardization. In this Review, we present systematic catalog different families spatial technologies; highlight their principles, power, limitations; give perspective suggestions on biggest challenges lay ahead incredibly powerful-but hard navigate-landscape.

Language: Английский

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Molecular and spatial signatures of mouse brain aging at single-cell resolution

Cell, Journal Year: 2022, Volume and Issue: 186(1), P. 194 - 208.e18

Published: Dec. 28, 2022

The diversity and complex organization of cells in the brain have hindered systematic characterization age-related changes its cellular molecular architecture, limiting our ability to understand mechanisms underlying functional decline during aging. Here, we generated a high-resolution cell atlas aging within frontal cortex striatum using spatially resolved single-cell transcriptomics quantified gene expression spatial major types these regions over mouse lifespan. We observed substantially more pronounced state, expression, non-neuronal neurons. Our data revealed signatures glial immune activation aging, particularly enriched subcortical white matter, identified both similarities notable differences cell-activation patterns induced by systemic inflammatory challenge. These results provide critical insights into inflammation brain.

Language: Английский

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Molecularly defined and spatially resolved cell atlas of the whole mouse brain

Nature, Journal Year: 2023, Volume and Issue: 624(7991), P. 343 - 354

Published: Dec. 13, 2023

In mammalian brains, millions to billions of cells form complex interaction networks enable a wide range functions. The enormous diversity and intricate organization have impeded our understanding the molecular cellular basis brain function. Recent advances in spatially resolved single-cell transcriptomics enabled systematic mapping spatial molecularly defined cell types tissues1-3, including several regions (for example, refs. 1-11). However, comprehensive atlas whole is still missing. Here we imaged panel more than 1,100 genes approximately 10 million across entire adult mouse brains using multiplexed error-robust fluorescence situ hybridization12 performed resolved, expression profiling at whole-transcriptome scale by integrating hybridization RNA sequencing data. Using this approach, generated 5,000 transcriptionally distinct clusters, belonging 300 major types, with high resolution. Registration common coordinate framework allowed quantifications cell-type composition individual regions. We further identified modules characterized compositions gradients featuring gradual changes cells. Finally, high-resolution map cells, each transcriptome-wide profile, us infer cell-type-specific interactions between hundreds pairs predict (ligand-receptor) functional implications these cell-cell interactions. These results provide rich insights into architecture foundation for investigations neural circuits their dysfunction health disease.

Language: Английский

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