16 Nature releases a map of brain motor cortex cells

Written | November, Xi's brain structure is extremely delicate and complex.
The tools developed at this stage can analyze the composition of different cell types in the brain
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As a result, scientists have established the cerebral cortex motor neuron map landscape and the database alliance BICCN (BRAIN Initiative Cell Census Network)
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On October 6, 2021, BICCN simultaneously published 16 articles on Nature, announcing the success of the initial research, and also distributed a viewpoint article A census of cell types in the brain's motor cortex by Johan Winnubst and Silvia Arber
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This report will introduce this viewpoint article in detail, and briefly introduce 16 research Nature articles (see BioArt follow-up report for details)
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 Johan Winnubst: "Workers must first sharpen their tools if they want to do good work"-a tool for building a map of cortical neuron composition The completion of the body's precise activities
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How to classify neurons with similar characteristics and what is the panorama of neuron diversity is still an important topic of neurobiology at present
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However, it is not easy to solve this problem
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To this end, scientists have established the BICCN, a consortium for the census of brain neuron cells, and established a map of primary motor neurons in the cerebral cortex
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The map includes data related to the molecules, functions, and physical states of neurons in the brains of mice, non-human primates, and humans (Figure 1)
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 Figure 1 The map of cerebral cortex motor neurons.
Single-cell RNA sequencing technology scRNA-seq is a technology used to measure gene expression in a single cell.
It can characterize the diversity of neurons by generating gene expression profiles of thousands of cells at a time
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A key strategy in the BICCN alliance is to use high-resolution scRNA-seq technology to analyze neuronal diversity in the cerebral cortex
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For example, the MERFISH technology used in the article jointly published by BICCN can be used to label genes in mouse brain tissue to determine the spatial position of these different cell types in the primary motor cortex
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In addition, the BICCN alliance has also established Patch-seq, which can record the electrical characteristics of neurons, and then scRNA-seq can be performed on these cells and combined with the reconstruction of their three-dimensional morphological structure
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In addition, BICCN also analyzes the epigenetic modifications in motor neurons, and at the same time projects the groups of these cells according to epigenetic characteristics, so that different cell groups can be analyzed
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 In addition, what is the origin of neuronal diversity in the development and evolution of the mammalian brain? In order to solve this problem, the article published by BICCN studied the epigenetic modification of neuron types across species, and epigenetic modification is defined by the pattern of gene expression
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Researchers combine the gene expression data with the abundance of methylation on the DNA of a single cell and the DNA accessibility in the DNA-protein complex of chromatin to program the positive and negative regulation of gene transcription in different neurons Analyze
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In addition, research in the BICCN Consortium has confirmed the potential regulatory regions of the genomes of different cell types
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These cell-type-specific transcription factor enrichment sites and binding sites are highly conserved across species and can be used to generate genetic tools for further studying the diversity of different neurons.
Therefore, the work in BICCN can mark a wide range of transcription subtypes.
Features
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 In addition, the work in the BICCN alliance emphasizes that in order to have a deeper understanding of the cell diversity of the brain, it is necessary to introduce new concepts and establish a new mathematical framework model
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For example, how to build a new mathematical model to describe the subtle differences between different cell subtypes and continuous gradients related to spatial locations
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 Although many of the technologies in the BICCN Alliance have been applied, these technologies were used for the first time in the establishment of such a highly collaborative, high-throughput database and map, providing an unprecedented diverse landscape of motor neurons
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In addition, the alliance opened the database to the public (https://biccn.
org), and built software that can be directly applied, so as to ensure that these data can be of great benefit to the research on the nature and origin of neuronal diversity.
The database falls into the actual use of scientific research
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 Silvia Arber: The "Census" of Motor Neuron Diversity-the high diversity and complexity of cell types in the brain that will be studied in the future has brought huge challenges to the neuroscience community
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By constructing such a huge database atlas, the BICCN Alliance provides a new and more comprehensive reference for the definition of cortical neuron cell types and how the cells are connected on the neural network
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There are three reasons for choosing the motor neuron cortex: First, the neuron projection in this area extends to many other parts of the motor system, but how this area interacts with other areas is still unknown.
There is still a promising "black box" area; second, the motor cortex controls the body's movement, so it understands the direct connection between different neuron cell types and functions; third, from an evolutionary perspective, the size and cell type of the area Diversity and functions are quite different among different species, so the evolution process of neuronal diversity in the motor cortex can be explored
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 As a result, neuroscientists will have access to databases containing many aspects of information about different types of cells in the motor cortex of different species, including cell gene expression, epigenetic modifications, cell morphology, and electrophysiological characteristics
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At the same time, the BICCN Alliance has also constructed a variety of mouse strains that can mark specific neuron populations or the activities of specific motor neurons in the control department through genetic manipulation
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The development of these tools will help uncover the connection between these motor neurons and their corresponding functions
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 There are two main types of mainstream cognition about the interaction mode of cortical neurons.
One is that cortical neurons only communicate with cortical neurons, and the other is that cortical neurons also communicate with other neurons
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The work in the BICCN alliance can study the interactions between cortical neurons in the brain's neural circuits, so as to determine how these neurons promote the learning, control and execution of movements and how these movements are carried out at the level of the nervous system.
Of
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 The "census" of motor neurons conducted by the BICCN alliance gave these neurons a clear identity and covered the development history of cortical neurons, including the mature development trajectory, plasticity and dynamic changes of these neurons
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The genetic program that runs during the development of the body is essential to determine the basic properties of neuronal cell types, such as basic functional properties such as neurotransmitter release or discharge characteristics
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The work in the BICCN consortium can improve the ability of researchers to target and label different cell types in mice
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In addition, the research in BICCN also includes a comparison of cell types in different species
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These methods help to understand the key neuron cell types from which cells evolved, which cell types are evolutionary "icing on the cake" additional cells for the fine activity of the cerebral cortex, and the molecular mechanisms that promote the emergence of new evolutionary functions
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 The work in BICCN points to the real treasure of the future
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This database provides a research database and operation platform for how the motor neural circuit is carried out.
At the same time, these work are essential for formulating specific cell types of brain disease treatment plans, and will ultimately help the research of clinical medical methods and the development of drugs.
To achieve the purpose of personalized medical treatment of "referring to where to fight" and "medicating to cure disease"
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Recall that 150 years ago, neurobiological research found that electrical stimulation of a certain area of ​​the cerebral cortex can induce motor behavior.
Since then, neuroscience has opened a new page
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The following are 16 Nature briefs (for detailed interpretation, please refer to the later related content) 1 The first Nature is from the BRAIN Initiative Cell Census Netword (BICCN), and the title is A multimodal cell census and atlas of the mammalian primary motor cortex
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This article outlines the work of BICCN, which is to draw a multi-level and multi-modal cell map of the mammalian initial motor cortex
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This work includes: 1) Delineating the molecular genetic landscape in motor cortex cells using multi-omics of transcriptome, chromatin accessibility group, and methylation group; 2) Cross-species analysis reveals that from mice to marmosets to humans Conservation of cell types; 3) In situ single-cell omics reveals the spatial atlas of the motor cortex; 4) Cross-pattern analysis reveals the physiological and anatomical characteristics and genomic basis of neurons
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In short, BICCN's work has constructed a neuron type framework that combines multi-dimensional information such as molecular information, spatial information, and phenotypic information
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2 The corresponding authors of the second article are Eran A.
Mukamel and Hongkui Zeng, and the title is A transcriptomic and epigenomic cell atlas of the mouse primary motor cortex
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In this work, the authors constructed a single-cell transcriptome and methylome of more than 500,000 cells in the primary motor cortex of mice, and described more than 56 neuron types
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3 The third article is from Ed S.
Lein and Trygve E.
Bakken, and the title is Comparative cellular analysis of motor cortex in human, marmoset and mouse
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This work performed transcriptome and episet sequencing on a total of more than 450,000 cells in the primary motor cortex of mice, marmosets, and humans, revealing the conservation of neuron types in the primary motor cortex in different species, as well as various The uniqueness between species
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4 The fourth article is from Ed Lein, and the title is Human neocortical expansion involves glutamatergic neuron diversification
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The research used patch-clamp technology, biocytin staining and single-cell sequencing platform Patch-Seq to detect the human neocortex, showing the consistency of five glutamatergic neurons in morphology, physiology, and gene expression, revealing The abundance of neuron types in the cortex
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5 The fifth article is from Joseph R.
Ecker, titled DNA methylation atlas of the mouse brain at single-cell resolution
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This work performed DNA methylation sequencing on a total of 103,982 cells in 45 regions in the mouse cortex, hippocampus, striatum, globus pallidus, and olfactory area, and constructed a neuronal methylation map and network in different brain regions.
The combination of methylation group and chromatin accessibility group data depicts the apparent basis of neuronal diversity and spatial organization in the mouse brain
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6 The sixth article comes from Ren Bing, and the title is An atlas of gene regulatory elements in adult mouse cerebrum
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This work studied the chromatin accessibility of more than 800,000 cells in 45 regions of the homomorphic cortex, olfactory bulb, hippocampus, and brain nucleus of adult mice, and constructed a cis-acting element regulation map of more than 160 different cell types
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7 The seventh chapter comes from Zhuang Xiaowei, and the title is Spatially resolved cell atlas of the mouse primary motor cortex by MERFISH
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This work used MERFISH (single-cell transcriptome-imaging method, multiplexed error-robust fluorescence in situ hybridization) to analyze a total of about 300,000 cells in the mouse primary motor cortex and adjacent areas, and identified 95 neurons/non-neurons.
The cell mass depicts the complex spatial network of the primary motor cortex
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8 The eighth article is from Hong-Wei Dong, Julie Harris, Pavel Osten, Z.
Josh Huang and Giorgio Ascoli, and the title is Cellular anatomy of the mouse primary motor cortex
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The work used gene labeling, sequencing, whole-brain imaging and other technologies to construct a 3D structure map of mouse primary motor cortex, upper limb area (MOp-ul).
24 projection neuron types were defined in this area and mapped Input-output neuron network
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9The ninth chapter is from Hong-Wei Dong, and the title is The mouse cortico–basal ganglia–thalamic network
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This work identified six parallel cortical-basal nucleus-thalamic networks
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10 The tenth chapter is from Edward Callaway and Joseph Ecker, titled Epigenomic diversity of cortical projection neurons in the mouse brain
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This work used retrograde labeling and single-nuclear DNA methylation sequencing to detect 11,827 neocortical neurons projecting from 63 cortex-cortex and cortex-subcortical distances, linking molecular features to neuronal anatomy and projection characteristics Get up
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11 The eleventh chapter is from Hongkui Zeng and Hanchuan Peng, and the title is Morphological diversity of single neurons in molecularly defined cell types
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This work reconstructed 1,741 neurons in the cortex, nucleus plexus, thalamus, and striatum, identified 11 types of projection neurons with different shape characteristics and gene expression characteristics, and revealed their cellular diversity
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12 The twelfth chapter is from Z.
Josh Huang, titled Genetic dissection of the glutamatergic neuron system in cerebral cortex
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By constructing a variety of transiently inducible Cre Flp knock-in mice, this work analyzed in detail the fate maps of different subgroups of pyramidal neurons and revealed the hierarchical differentiation trajectory of pyramidal neurons
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13 The thirteenth article is from Lior Pachter, titled Isoform cell-type specificity in the mouse primary motor cortex
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The study performed SMART-Seq on 6,160 cells in the primary motor cortex of mice, 280,327 cells were subjected to MERFISH, and 94,162 cells were subjected to 10x Genomic single-cell sequencing, revealing isoforms in different cell types.
), and its transformation, reveals the function of homologous isomers in identifying cell types
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14 The fourteenth article is from Arnold R.
Kriegstein, titled An atlas of cortical arealization identifies dynamic molecular signatures
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The study used single-cell sequencing to study 10 main brain regions and 6 neocortical regions in the stages of neurodevelopment and early glial production, revealing the molecular maps of the longitudinal development of different cells in different cortical regions
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15 The fifteenth chapter is from Tomasz J.
Nowakowski, titled Single-cell epigenomics reveals mechanisms of human cortical development
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This work uses single-cell ATAC-seq to analyze the gene locus and regulatory element maps of different cell types during human cortex development, revealing the diversity of neuron progenitor cells in the cerebral cortex
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16 The sixteenth chapter is from Evan Macosko, titled A transcriptomic atlas of mouse cerebellar cortex comprehensively defines cell types
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The study used high-throughput sequencing to study the molecular maps of different cell types in different lobes of the mouse cerebellum, revealing the unique molecular characteristics of different cell types, and linking these characteristics with physiological characteristics
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