A collective international effort has culminated in the most expansive atlas of the primate brain, consisting of 4.2 million cells. This atlas not only reveals specific functionalities within distinct regions of the brain but also has implications for understanding neurological disorders, thereby setting the stage for future advancements in brain science.
With more than 4 million cells cataloged, this atlas stands as the largest to date, offering new insights into human brain evolution as well as potential avenues for disease intervention and therapy.
One of the enduring enigmas in scientific research is understanding how over 100 million individual neurons coalesce to create a network that constitutes the basis for human cognition, emotion, and actions.
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An International Initiative to Map the Brain
The endeavor to map these intricate cell clusters and comprehend their roles has been a long-term objective of numerous molecular cartographers around the globe, participating under the umbrella of the National Institutes of Health’s “Brain Initiative Cell Census Network” project. The principal aim of this atlas is to facilitate the progress of neuroscience research. The aspiration is that this work will enable researchers to deepen their understanding of conditions such as autism and depression.
Pioneering Insights
Recent series of studies have now divulged the inner molecular mechanics of the brain at an unparalleled scale and level of detail.
To contribute to a broader understanding of the evolution of brains in humans and other animals, a research consortium led by experts from Arizona State University, the University of Pennsylvania, the University of Washington, and the Brotman Baty Institute, has generated the largest brain atlas encompassing the entire primate brain.
“Identifying the locations and functions of cells in the adult primate brain is essential both for understanding human cognitive and behavioral evolution, and for pinpointing what goes awry in cases of neurological disorders,” stated Noah Snyder-Mackler, senior co-author and associate professor at Arizona State University’s School of Life Sciences and Center for Evolution and Medicine.
The objective was to meticulously analyze a wide array of brain cells, both neurons and non-neurons, employing cutting-edge single-cell technology.
Utilizing samples from 30 disparate regions of the brain, they systematically constructed a new atlas, resulting in a comprehensive 4.2 million-cell map of the adult primate brain.
“Our publicly accessible data represents the most extensive and multi-faceted molecular atlas in a primate to date. This is critical for investigating how the brain’s numerous cells interact to produce the behavioral complexity of primates, including humans,” noted Jay Shendure, senior co-author and professor of Genome Sciences at the University of Washington and Director of the Brotman Baty Institute.
“These findings also furnish a detailed map for examining complex human-relevant social behavior and disease, as well as for identifying cellular and network similarities and differences across species,” added Michael Platt, another senior co-author and professor in the Departments of Neuroscience, Psychology, and Marketing at the University of Pennsylvania.
A Comprehensive Multi-Omic Analysis
In each cell nucleus, the scientists profiled gene expression (2.58 million transcriptomes) and examined a range of complementary DNA gene regulatory regions (1.59 million epigenomes). This “multi-omic” approach provided the basis to identify distinct brain cell types by their molecular blueprints, offering new avenues for detailed cellular studies.
The gene expression profiles led to the discovery of hundreds of molecularly distinct types of brain cells. They also found that cell composition varies considerably across the brain, manifesting in cellular markers of region-specific functions. This includes the neurotransmitters responsible for brain cell communication and the support cells that guard against diseases like Alzheimer’s.
Their research also probed 53 phenotypes pertinent to the risk of neurological diseases and other traits. Among their findings were cells implicated in leading neurological diseases such as cardioembolic or ischemic stroke.
Furthermore, genes associated with Alzheimer’s disease were found predominantly in the DNA regulatory regions that are accessible only in microglia, the primary immune cells of the brain, corroborating their significant role in Alzheimer’s disease as determined from genome-wide association studies.
Remarkably, the researchers identified new regulatory regions, allowing them to delve into the genetic structure of neurological disease risk at a cellular level. “We found multiple associations between genetic susceptibility for neurological disorders and the epigenomic statuses of specific cell types, some of which were previously unconnected,” said Kenneth Chiou, co-lead author and postdoc at ASU.
Another cell class of interest, basket cells, showed enrichment for a variety of genome-wide association study phenotypes, including conditions like schizophrenia, bipolar disorder, major depressive disorder, and most prominently, epilepsy.
They also discovered that genes associated with attention deficit/hyperactivity disorder (ADHD) were particularly enriched among open regions of medium spiny neurons, which have been implicated in behavioral hyperactivity and attention disruption.
In summary, this multi-omic atlas now serves as a public resource, enabling researchers globally to delve further into the intricacies of human brain evolution and to pinpoint new pathways for intervention in neurological diseases.
Reference: “A single-cell multi-omic atlas spanning the adult rhesus macaque brain” by Kenneth L. Chiou et al., published on 12 October 2023 in Science Advances.
DOI: 10.1126/sciadv.adh1914
Frequently Asked Questions (FAQs) about Comprehensive Primate Brain Atlas
What is the primary focus of this comprehensive primate brain atlas?
The primary focus of this atlas is to provide an in-depth understanding of the primate brain, consisting of 4.2 million cells. It aims to advance neuroscience research, offer insights into the evolution of the human brain, and open new avenues for understanding and treating neurological diseases.
Who are the main institutions involved in this project?
The main institutions involved are Arizona State University, the University of Pennsylvania, the University of Washington, and the Brotman Baty Institute. They collaborated in generating the most expansive atlas of the primate brain to date.
What is the main goal of mapping these cells?
The main goal is to facilitate the progress of neuroscience research. Specifically, the project aims to deepen our understanding of how individual neurons contribute to cognition, emotion, and behaviors in primates, including humans.
What technology was used for this research?
State-of-the-art single-cell technology was employed to identify and analyze a wide array of brain cells, both neurons and non-neurons. The researchers also used multi-omic analysis to profile gene expression and examine DNA regulatory regions in each cell nucleus.
How will this atlas benefit future research into neurological disorders?
The atlas will serve as a foundational resource for researchers globally, enabling them to delve into the intricacies of human brain evolution and neurological diseases. It offers potential pathways for interventions and treatments for conditions such as Alzheimer’s, ADHD, epilepsy, and various other neurological disorders.
Is the data from this research publicly accessible?
Yes, the data is publicly accessible and has been made available to the scientific community and the broader public. The researchers intend for it to be used to further explore how the many cells of the brain contribute to the behavioral complexity of primates, including humans.
What are some groundbreaking discoveries made through this research?
The researchers discovered hundreds of molecularly distinct types of brain cells and found that cell composition varies significantly across different regions of the brain. They also identified new genetic regulatory regions that may be involved in neurological diseases, providing a detailed genetic architecture at the cellular level for neurological disease risk.
What are the implications for diseases like Alzheimer’s and ADHD?
Genes linked to Alzheimer’s disease were found to be predominantly present in the DNA regulatory regions accessible only in microglia, the primary immune cells of the brain. For ADHD, the researchers found that medium spiny neurons may be a promising new target for future studies, as these neurons have been linked to behavioral hyperactivity and disrupted attention.
Who are the senior co-authors of the research?
The senior co-authors include Noah Snyder-Mackler, an associate professor at Arizona State University’s School of Life Sciences and Center for Evolution and Medicine; Jay Shendure, a professor of Genome Sciences at the University of Washington and Director of the Brotman Baty Institute; and Michael Platt, a professor in the Departments of Neuroscience, Psychology, and Marketing at the University of Pennsylvania.
More about Comprehensive Primate Brain Atlas
- Comprehensive Primate Brain Atlas Project
- National Institutes of Health’s Brain Initiative
- State-of-the-Art Single-Cell Technologies in Neuroscience
- Multi-Omic Analysis in Neurological Research
- Arizona State University’s School of Life Sciences
- University of Pennsylvania’s Department of Neuroscience
- University of Washington’s Genome Sciences Department
- Brotman Baty Institute’s Research Focus
- Overview of Neurological Disorders
- Open Access Data in Neuroscience Research
5 comments
This could be a game changer for treating neurological diseases. Imagine, actual targeted treatments for Alzheimer’s and ADHD. So hopeful right now.
Wow, this is mind-blowing stuff! I mean 4.2 million cells mapped. What a leap for neuroscience.
totally amazed by the tech used here. Single-cell technologies and multi-omic analysis? we’re living in the future folks.
A global effort for a global issue. Hats off to all the institutions involved. ASU, Univ of Penn, Univ of Wash, and Brotman Baty Institute, you guys are heroes.
Open access data is the way to go. It speeds up further research and who knows what other breakthroughs we might see cuz of it.