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Written | November https:// October 6, 2021, the cerebral cortex motor neuron map landscape and the database alliance will be published on Nature at the same time 16 articles (sixteen of Nature's heavy release of the brain motor cortex cell map), uncovered the map landscape of multiple levels in the motor neuron cortex
.
The first of these 16 articles is the BICCN Consortium (BRAIN Initiative Cell Census Network) for this multi-country and multi-research group collaboration.
The article is titled A multimodal cell census and atlas of the mammalian primary motor cortex, outlines the single-cell transcriptome, chromatin accessibility, DNA methylome, spatial resolution single-cell transcriptome, and morphology in the cortex of a variety of mammalian motor neurons The large-scale analysis of biological and electrophysiological characteristics and cell resolution input and output maps has established a unified mechanism framework for neuronal cell organization, integrating multiple layers of molecular genetic and spatial information with various phenotypic characteristics
.
The human brain is a huge network composed of different information processing units.
It is different from other organs of the human body.
The brain is composed of billions of neurons, which are connected to each other through trillions of synapses to promote human learning and memory.
And the conduct of complex activities
.
The key step in understanding the structure, development, function, and disease of the brain is to discover and map the characteristic landscape of neurons and other cell types
.
The diversity of neurons has always been a problem that scientists want to uncover.
Neurons have similar properties and are the basic units in the brain circuit.
However, it is still huge to quantify and define the types of neurons.
The challenge [1,2]
.
Many traditional techniques can only analyze one or a small group of neurons at a time.
Therefore, the need for a global overview of neuron species is coming
.
At the same time, single-cell genomics technology provides an unparalleled high-resolution and high-throughput technology platform for biological research, which can be used to uncover the transcriptome and epigenetic maps in a single cell, and quickly It affects the analysis of cell composition types in many disciplines including neurobiology
.
The use of single-cell RNA sequencing methods on the surface of the cerebral cortex and other areas of the brain reveals the complex transcriptome features of different cell types.
These features are consistent with the anatomical experience accumulated by scientists for decades, but the resolution is low.
The precision is beyond the reach of traditional anatomy and immunostaining techniques
.
The goal of the cell census network established by the BICCN Alliance is to use these technologies to generate an open-access map of brain neuron cortex cells, which contains molecular, spatial, morphological, connection, and functional data, which can be used for mice, humans, and non- Human primates are described [3]
.
The census of brain neurons is similar to the population census.
It is used to define the different cell types and their proportions, spatial distribution, and phenotypic characteristics in the cortex of motor neurons in the brain, so as to provide new ideas for everyone to understand the brain's operation mode and tissue function.
Platform
.
In the general remarks, the BICCN Alliance summarized the findings during the establishment of the brain neuron cortex map.
The main findings include: integrating gene expression, chromatin status, and DNA methylation modification, combined with single-cell transcriptomics And epigenomics analysis reveals the cell composition type of motor neuron cortex and unifies the molecular genetic pattern of neuronal cortex; cell types are generated through single-cell omics, spatial analysis of single-cell transcriptomics based on MERFISH, and Patch-seq Atlas, established the spatial distribution of different cell types in different cortex and cortical sublayers; comparatively analyzed the brain motor neuron cortex in mice, marmosets and humans, and analyzed the developmental origin and hierarchical organization of the motor neuron cortex across species.
Describe the transcriptional similarity between different species; compare the highly conserved cell identity transcriptome and epigenome characteristics across species, which proves the high evolutionary specialization of motor cortex neurons; agreement between molecular, anatomical and physiological data Sex can better classify different neuron types, and at the same time reveal the evolution process between different types of neurons; define the characteristics of the input and output connections of neuronal cells defined by the main transcriptome; excite neurons The complex correspondence between the long-range axon projection pattern and the transcriptome and epigenetic group indicates that there are other levels of regulation in the specific connection of single cells; cell type transcription and epigenetic characteristics guide the glutamate pyramidal nerve The generation of genetic tools for the fate map of metatypes and their progenitor cell types; BICCN database realizes the creation of highly standardized, computationally integrated open database resources, which can provide data, tools and knowledge platforms for research and applications
.
The BICCN consortium obtained a map of mouse motor neuron cortex through seven single-cell RNA-seq and single-nuclear RNA-seq data, as well as mononuclear methylcytosine sequencing, and sequencing of mononuclear chromatin accessibility [4]
.
Through the integration and classification of databases in mice, humans and marmosets, the BICCN alliance identified 45 conserved cell types, including 24 gamma-aminobutyric acid neurons and 13 glutamatergic neurons And 8 non-neuronal types
.
In addition, the BICCN Alliance used the MERFISH experiment to identify cell types in situ, spatial positioning, and projection analysis, and used Patch-seq to map cross-species transcriptomes and morphological-electrophysiological characteristics in the motor neuron cortex (Figure 1)
.
Figure 1 Patch-seq identifies the transcriptome and morphological-electrophysiological characteristics of neurons.
In addition, the BICCN Alliance has also established a series of genetic tools that can target different types of glutamate vertebral neurons in the motor neuron cortex , Including 15 Cre and Flp drive lines
.
And through tracer, Cre strain labeling, single neuron reconstruction, high-resolution whole brain imaging, and computer analysis, a comprehensive single-cell resolution input and output neural circuit network diagram was established (Figure 2)
.
Figure 2 Corresponding maps of neural circuits.
Through the integrated analysis of these technologies, the BICCN alliance has constructed a complete cross-species motor neuron cortical map.
This map provides a basic platform for the broad neuroscience community to accumulate and The integration of cross-species cell type information also lays a foundation for understanding the molecular genetic programs of cell type specialization, maturation, and neural circuit assembly
.
Original link: https://doi.
org/10.
1038/s41586-021-03950-0 Platemaker: XI Reference 1 Zeng, H.
& Sanes, JR Neuronal cell-type classification: challenges, opportunities and the path forward.
Nature reviews.
Neuroscience 18, 530-546, doi:10.
1038/nrn.
2017.
85 (2017).
2 Mukamel, EA & Ngai, J.
Perspectives on defining cell types in the brain.
Current opinion in neurobiology 56, 61-68, doi :10.
1016/j.
conb.
2018.
11.
007 (2019).
3 Ecker, JR et al.
The BRAIN Initiative Cell Census Consortium: Lessons Learned toward Generating a Comprehensive Brain Cell Atlas.
Neuron 96, 542-557, doi:10.
1016/j .
neuron.
2017.
10.
007 (2017).
4 Yao, Z.
et al.
A transcriptomic and epigenomic cell atlas of the mouse primary motor cortex.
Nature 598, 103-110, doi:10.
1038/s41586-021-03500-8 ( 2021).
Reprinting instructions [Original Articles] BioArt original articles are welcome to be shared by individuals.
Reprinting is prohibited without permission.
The copyrights of all published works are owned by BioArt
.
BioArt reserves all statutory rights and offenders must be investigated
.
.
The first of these 16 articles is the BICCN Consortium (BRAIN Initiative Cell Census Network) for this multi-country and multi-research group collaboration.
The article is titled A multimodal cell census and atlas of the mammalian primary motor cortex, outlines the single-cell transcriptome, chromatin accessibility, DNA methylome, spatial resolution single-cell transcriptome, and morphology in the cortex of a variety of mammalian motor neurons The large-scale analysis of biological and electrophysiological characteristics and cell resolution input and output maps has established a unified mechanism framework for neuronal cell organization, integrating multiple layers of molecular genetic and spatial information with various phenotypic characteristics
.
The human brain is a huge network composed of different information processing units.
It is different from other organs of the human body.
The brain is composed of billions of neurons, which are connected to each other through trillions of synapses to promote human learning and memory.
And the conduct of complex activities
.
The key step in understanding the structure, development, function, and disease of the brain is to discover and map the characteristic landscape of neurons and other cell types
.
The diversity of neurons has always been a problem that scientists want to uncover.
Neurons have similar properties and are the basic units in the brain circuit.
However, it is still huge to quantify and define the types of neurons.
The challenge [1,2]
.
Many traditional techniques can only analyze one or a small group of neurons at a time.
Therefore, the need for a global overview of neuron species is coming
.
At the same time, single-cell genomics technology provides an unparalleled high-resolution and high-throughput technology platform for biological research, which can be used to uncover the transcriptome and epigenetic maps in a single cell, and quickly It affects the analysis of cell composition types in many disciplines including neurobiology
.
The use of single-cell RNA sequencing methods on the surface of the cerebral cortex and other areas of the brain reveals the complex transcriptome features of different cell types.
These features are consistent with the anatomical experience accumulated by scientists for decades, but the resolution is low.
The precision is beyond the reach of traditional anatomy and immunostaining techniques
.
The goal of the cell census network established by the BICCN Alliance is to use these technologies to generate an open-access map of brain neuron cortex cells, which contains molecular, spatial, morphological, connection, and functional data, which can be used for mice, humans, and non- Human primates are described [3]
.
The census of brain neurons is similar to the population census.
It is used to define the different cell types and their proportions, spatial distribution, and phenotypic characteristics in the cortex of motor neurons in the brain, so as to provide new ideas for everyone to understand the brain's operation mode and tissue function.
Platform
.
In the general remarks, the BICCN Alliance summarized the findings during the establishment of the brain neuron cortex map.
The main findings include: integrating gene expression, chromatin status, and DNA methylation modification, combined with single-cell transcriptomics And epigenomics analysis reveals the cell composition type of motor neuron cortex and unifies the molecular genetic pattern of neuronal cortex; cell types are generated through single-cell omics, spatial analysis of single-cell transcriptomics based on MERFISH, and Patch-seq Atlas, established the spatial distribution of different cell types in different cortex and cortical sublayers; comparatively analyzed the brain motor neuron cortex in mice, marmosets and humans, and analyzed the developmental origin and hierarchical organization of the motor neuron cortex across species.
Describe the transcriptional similarity between different species; compare the highly conserved cell identity transcriptome and epigenome characteristics across species, which proves the high evolutionary specialization of motor cortex neurons; agreement between molecular, anatomical and physiological data Sex can better classify different neuron types, and at the same time reveal the evolution process between different types of neurons; define the characteristics of the input and output connections of neuronal cells defined by the main transcriptome; excite neurons The complex correspondence between the long-range axon projection pattern and the transcriptome and epigenetic group indicates that there are other levels of regulation in the specific connection of single cells; cell type transcription and epigenetic characteristics guide the glutamate pyramidal nerve The generation of genetic tools for the fate map of metatypes and their progenitor cell types; BICCN database realizes the creation of highly standardized, computationally integrated open database resources, which can provide data, tools and knowledge platforms for research and applications
.
The BICCN consortium obtained a map of mouse motor neuron cortex through seven single-cell RNA-seq and single-nuclear RNA-seq data, as well as mononuclear methylcytosine sequencing, and sequencing of mononuclear chromatin accessibility [4]
.
Through the integration and classification of databases in mice, humans and marmosets, the BICCN alliance identified 45 conserved cell types, including 24 gamma-aminobutyric acid neurons and 13 glutamatergic neurons And 8 non-neuronal types
.
In addition, the BICCN Alliance used the MERFISH experiment to identify cell types in situ, spatial positioning, and projection analysis, and used Patch-seq to map cross-species transcriptomes and morphological-electrophysiological characteristics in the motor neuron cortex (Figure 1)
.
Figure 1 Patch-seq identifies the transcriptome and morphological-electrophysiological characteristics of neurons.
In addition, the BICCN Alliance has also established a series of genetic tools that can target different types of glutamate vertebral neurons in the motor neuron cortex , Including 15 Cre and Flp drive lines
.
And through tracer, Cre strain labeling, single neuron reconstruction, high-resolution whole brain imaging, and computer analysis, a comprehensive single-cell resolution input and output neural circuit network diagram was established (Figure 2)
.
Figure 2 Corresponding maps of neural circuits.
Through the integrated analysis of these technologies, the BICCN alliance has constructed a complete cross-species motor neuron cortical map.
This map provides a basic platform for the broad neuroscience community to accumulate and The integration of cross-species cell type information also lays a foundation for understanding the molecular genetic programs of cell type specialization, maturation, and neural circuit assembly
.
Original link: https://doi.
org/10.
1038/s41586-021-03950-0 Platemaker: XI Reference 1 Zeng, H.
& Sanes, JR Neuronal cell-type classification: challenges, opportunities and the path forward.
Nature reviews.
Neuroscience 18, 530-546, doi:10.
1038/nrn.
2017.
85 (2017).
2 Mukamel, EA & Ngai, J.
Perspectives on defining cell types in the brain.
Current opinion in neurobiology 56, 61-68, doi :10.
1016/j.
conb.
2018.
11.
007 (2019).
3 Ecker, JR et al.
The BRAIN Initiative Cell Census Consortium: Lessons Learned toward Generating a Comprehensive Brain Cell Atlas.
Neuron 96, 542-557, doi:10.
1016/j .
neuron.
2017.
10.
007 (2017).
4 Yao, Z.
et al.
A transcriptomic and epigenomic cell atlas of the mouse primary motor cortex.
Nature 598, 103-110, doi:10.
1038/s41586-021-03500-8 ( 2021).
Reprinting instructions [Original Articles] BioArt original articles are welcome to be shared by individuals.
Reprinting is prohibited without permission.
The copyrights of all published works are owned by BioArt
.
BioArt reserves all statutory rights and offenders must be investigated
.
