A taxonomy of transcriptomic cell types across the isocortex and hippocampal formation

Cell, Journal Year: 2021, Volume and Issue: 184(12), P. 3222 - 3241.e26

Published: May 17, 2021

Language: Английский

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Cell stress in cortical organoids impairs molecular subtype specification

Nature, Journal Year: 2020, Volume and Issue: 578(7793), P. 142 - 148

Published: Jan. 29, 2020

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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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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Brain organoids for the study of human neurobiology at the interface of in vitro and in vivo

Nature Neuroscience, Journal Year: 2020, Volume and Issue: 23(12), P. 1496 - 1508

Published: Nov. 2, 2020

Language: Английский

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Single-cell epigenomics reveals mechanisms of human cortical development

Nature, Journal Year: 2021, Volume and Issue: 598(7879), P. 205 - 213

Published: Oct. 6, 2021

Abstract During mammalian development, differences in chromatin state coincide with cellular differentiation and reflect changes the gene regulatory landscape 1 . In developing brain, cell fate specification topographic identity are important for defining 2 confer selective vulnerabilities to neurodevelopmental disorders 3 Here, identify cell-type-specific accessibility patterns human we used a single-cell assay transposase by sequencing (scATAC-seq) primary tissue samples from forebrain. We applied unbiased analyses genomic loci that undergo extensive cell-type- brain-region-specific during neurogenesis, an integrative analysis predict candidate elements. found cerebral organoids recapitulate most putative enhancer but lack many open regions vivo. Systematic comparison of across brain revealed unexpected diversity among neural progenitor cells cortex implicated retinoic acid signalling neuronal lineage prefrontal cortex. Together, our results reveal contribution emerging type provide blueprint evaluating fidelity robustness as model cortical development.

Language: Английский

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An atlas of cortical arealization identifies dynamic molecular signatures

Nature, Journal Year: 2021, Volume and Issue: 598(7879), P. 200 - 204

Published: Oct. 6, 2021

Abstract The human brain is subdivided into distinct anatomical structures, including the neocortex, which in turn encompasses dozens of specialized cortical areas. Early morphogenetic gradients are known to establish early regions and areas, but how patterns result finer more discrete spatial differences remains poorly understood 1 . Here we use single-cell RNA sequencing profile ten major structures six neocortical areas during peak neurogenesis gliogenesis. Within find that second trimester, a large number genes differentially expressed across all cell types, radial glia, neural progenitors cortex. However, abundance areal transcriptomic signatures increases as glia differentiate intermediate progenitor cells ultimately give rise excitatory neurons. Using an automated, multiplexed single-molecule fluorescent situ hybridization approach, laminar gene-expression highly dynamic regions. Together, our data suggest patterning defined by strong, mutually exclusive frontal occipital signatures, with resulting giving specification between these two poles throughout successive developmental timepoints.

Language: Английский

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Human brain organogenesis: Toward a cellular understanding of development and disease

Cell, Journal Year: 2021, Volume and Issue: 185(1), P. 42 - 61

Published: Nov. 11, 2021

Language: Английский

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Pathogenic DDX3X Mutations Impair RNA Metabolism and Neurogenesis during Fetal Cortical Development

Neuron, Journal Year: 2020, Volume and Issue: 106(3), P. 404 - 420.e8

Published: March 4, 2020

Language: Английский

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Broad transcriptomic dysregulation occurs across the cerebral cortex in ASD

Nature, Journal Year: 2022, Volume and Issue: 611(7936), P. 532 - 539

Published: Nov. 2, 2022

Abstract Neuropsychiatric disorders classically lack defining brain pathologies, but recent work has demonstrated dysregulation at the molecular level, characterized by transcriptomic and epigenetic alterations 1–3 . In autism spectrum disorder (ASD), this pathology involves upregulation of microglial, astrocyte neural–immune genes, downregulation synaptic attenuation gene-expression gradients in cortex 1,2,4–6 However, whether these changes are limited to cortical association regions or more widespread remains unknown. To address issue, we performed RNA-sequencing analysis 725 samples spanning 11 areas from 112 post-mortem individuals with ASD neurotypical controls. We find across ASD, exhibiting an anterior-to-posterior gradient, greatest differences primary visual cortex, coincident typical between regions. Single-nucleus methylation profiling demonstrate that robust signature reflects cell-type-specific gene expression, particularly affecting excitatory neurons glia. Both rare common ASD-associated genetic variation converge within a downregulated co-expression module involving signalling, alone is enriched upregulated protein chaperone genes. These results highlight cerebral extending beyond broadly involve sensory

Language: Английский

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