Spatially resolved cell atlas of the mouse primary motor cortex by MERFISH

Nature, Journal Year: 2021, Volume and Issue: 598(7879), P. 137 - 143

Published: Oct. 6, 2021

Abstract A mammalian brain is composed of numerous cell types organized in an intricate manner to form functional neural circuits. Single-cell RNA sequencing allows systematic identification based on their gene expression profiles and has revealed many distinct populations the 1,2 . epigenomic profiling 3,4 further provides information gene-regulatory signatures different types. Understanding how contribute function, however, requires knowledge spatial organization connectivity, which not preserved sequencing-based methods that involve dissociation. Here we used a single-cell transcriptome-imaging method, multiplexed error-robust fluorescence situ hybridization (MERFISH) 5 , generate molecularly defined spatially resolved atlas mouse primary motor cortex. We profiled approximately 300,000 cells cortex its adjacent areas, identified 95 neuronal non-neuronal clusters, complex map only excitatory but also most inhibitory clusters adopted laminar organizations. Intratelencephalic neurons formed largely continuous gradient along cortical depth axis, individual correlated with depths. Furthermore, integrated MERFISH retrograde labelling probe projection targets found projections network project multiple target regions receive inputs from clusters.

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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Cellular anatomy of the mouse primary motor cortex

Nature, Journal Year: 2021, Volume and Issue: 598(7879), P. 159 - 166

Published: Oct. 6, 2021

An essential step toward understanding brain function is to establish a structural framework with cellular resolution on which multi-scale datasets spanning molecules, cells, circuits and systems can be integrated interpreted

Language: Английский

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Inflammation From Peripheral Organs to the Brain: How Does Systemic Inflammation Cause Neuroinflammation?

Frontiers in Aging Neuroscience, Journal Year: 2022, Volume and Issue: 14

Published: June 16, 2022

As inflammation in the brain contributes to several neurological and psychiatric diseases, cause of neuroinflammation is being widely studied. The causes can be roughly divided into following domains: viral infection, autoimmune disease, from peripheral organs, mental stress, metabolic disorders, lifestyle. In particular, effects caused by organs have yet unclear mechanisms. Many such as gastrointestinal inflammation, chronic obstructive pulmonary rheumatoid arthritis, dermatitis, fatigue syndrome, or myalgic encephalomyelitis (CFS/ME), trigger through pathways. mechanisms action for inflammation-induced include disruption blood-brain barrier, activation glial cells associated with systemic immune activation, on autonomic nerves via organ-brain axis. this review, we consider previous studies relationship between neuroinflammation, focusing regions susceptible inflammation.

Language: Английский

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Single-cell and spatial transcriptomics: deciphering brain complexity in health and disease

Nature Reviews Neurology, Journal Year: 2023, Volume and Issue: 19(6), P. 346 - 362

Published: May 17, 2023

Language: Английский

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Genetic dissection of the glutamatergic neuron system in cerebral cortex

Nature, Journal Year: 2021, Volume and Issue: 598(7879), P. 182 - 187

Published: Oct. 6, 2021

Diverse types of glutamatergic pyramidal neurons mediate the myriad processing streams and output channels cerebral cortex

Language: Английский

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Comparative transcriptomics reveals human-specific cortical features

Science, Journal Year: 2023, Volume and Issue: 382(6667)

Published: Oct. 12, 2023

The cognitive abilities of humans are distinctive among primates, but their molecular and cellular substrates poorly understood. We used comparative single-nucleus transcriptomics to analyze samples the middle temporal gyrus (MTG) from adult humans, chimpanzees, gorillas, rhesus macaques, common marmosets understand human-specific features neocortex. Human, chimpanzee, gorilla MTG showed highly similar cell-type composition laminar organization as well a large shift in proportions deep-layer intratelencephalic-projecting neurons compared with macaque marmoset MTG. Microglia, astrocytes, oligodendrocytes had more-divergent expression across species or oligodendrocyte precursor cells, neuronal diverged more rapidly on human lineage. Only few hundred genes patterning, suggesting that relatively changes distinctively define cortical structure.

Language: Английский

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Axonal energy metabolism, and the effects in aging and neurodegenerative diseases

Molecular Neurodegeneration, Journal Year: 2023, Volume and Issue: 18(1)

Published: July 20, 2023

Abstract Human studies consistently identify bioenergetic maladaptations in brains upon aging and neurodegenerative disorders of (NDAs), such as Alzheimer’s disease, Parkinson’s Huntington’s Amyotrophic lateral sclerosis. Glucose is the major brain fuel glucose hypometabolism has been observed regions vulnerable to NDAs. Many susceptible are topological central hub connectome, linked by densely interconnected long-range axons. Axons, key components have high metabolic needs support neurotransmission other essential activities. Long-range axons particularly injury, neurotoxin exposure, protein stress, lysosomal dysfunction, etc. Axonopathy often an early sign neurodegeneration. Recent ascribe axonal maintenance failures local dysregulation. With this review, we aim stimulate research exploring metabolically oriented neuroprotection strategies enhance or normalize bioenergetics NDA models. Here start summarizing evidence from human patients animal models reveal correlation between connectomic disintegration aging/NDAs. To encourage mechanistic investigations on how dysregulation occurs during aging/NDAs, first review current literature distinct subdomains: axon initial segments, myelinated arbors harboring pre-synaptic boutons. In each subdomain, focus organization, activity-dependent regulation system, external glial support. Second, mechanisms regulating nicotinamide adenine dinucleotide (NAD + ) homeostasis, molecule for energy metabolism processes, including NAD biosynthetic, recycling, consuming pathways. Third, highlight innate vulnerability connectome discuss its perturbation As deficits developing into NDAs, especially asymptomatic phase, they likely exaggerated further impaired energetic cost neural network hyperactivity, pathology. Future interrogating causal relationship vulnerability, axonopathy, amyloid/tau pathology, cognitive decline will provide fundamental knowledge therapeutic interventions.

Language: Английский

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Regional and cell-type-specific afferent and efferent projections of the mouse claustrum

Cell Reports, Journal Year: 2023, Volume and Issue: 42(2), P. 112118 - 112118

Published: Feb. 1, 2023

The claustrum (CLA) is a conspicuous subcortical structure interconnected with cortical and regions. Its regional anatomy cell-type-specific connections in the mouse remain not fully determined. Using multimodal reference datasets, we confirmed delineation of CLA as single group neurons embedded agranular insular cortex. We quantitatively investigated brain-wide inputs outputs using bulk anterograde retrograde viral tracing data neuron data. found that prefrontal module has more cell types projecting to than other modules, layer 5 IT predominating. nine morphological principal topographically innervate functionally linked targets, preferentially midline areas, secondary motor area, entorhinal area. Together, this study provides detailed wiring diagram CLA, laying foundation for studying its functions at cellular level.

Language: Английский

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