In a significant joint endeavor spearheaded by the University of California San Diego (UCSD), scientists have scrutinized over a million human brain cells to construct intricate mappings of gene regulatory elements across different types of brain cells. This research, an integral component of the BRAIN Initiative, underscores the association between particular cellular types and common neuropsychiatric conditions. Additionally, the researchers utilized artificial intelligence to project the repercussions of specific gene variants considered high-risk.
Researchers Explore Associations of Gene Regulatory Elements and Cell Types with Conditions like Schizophrenia, Alzheimer’s, and Bipolar Disorder
In this expansive collaboration involving multiple institutions and led by UCSD, the research team pored over more than a million cells from human brains to develop detailed blueprints of gene regulatory elements across varied brain cell types. They also established connections between these specific cell types and several widespread neuropsychiatric disorders. Advanced artificial intelligence methodologies were employed to estimate the effects of singular high-risk gene variants and their potential contributions to diseases.
“The brain is not a monolithic entity but a complex tapestry of different cell types, each with distinct appearances and roles. Deciphering these diverse cell types and understanding their functionalities is crucial for uncovering new therapeutic strategies that can be tailored to individual diseases,” stated Bing Ren, Ph.D.
Objectives of the BRAIN Initiative
The pivotal study, published in a dedicated issue of Science on October 13, 2023, is an element of the National Institute of Health’s Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative, inaugurated in 2014. The agenda of this initiative is to fundamentally alter our comprehension of the mammalian brain, partly by cultivating groundbreaking neurotechnologies to characterize distinct neural cell types.
Deciphering Cellular Variability
Although every cell in the human brain shares the same DNA sequence, different cell types activate distinct genes and in varied quantities. This leads to a multitude of brain cell types, further complicating the architecture of neural circuits. Understanding these cellular differences on a molecular level is indispensable for gaining insights into the brain’s functioning and devising new treatment options for neuropsychiatric disorders.
Complexity of Brain Architecture
“The brain is far from being a uniform structure,” remarked Bing Ren, Ph.D., professor at UC San Diego School of Medicine. “It consists of an incredibly intricate network of neurons and other non-neuronal cells, each performing different roles. Unpacking these cell types and comprehending their interplay is crucial for identifying novel therapeutic avenues targeting specific cell types germane to individual diseases.”
Key Takeaways from the Study
In this recent investigation, the team examined over 1.1 million brain cells across 42 unique brain regions obtained from three different human brains. They discerned 107 distinct subcategories of brain cells and related specific aspects of their molecular biology to a broad array of neuropsychiatric maladies such as schizophrenia, bipolar disorder, Alzheimer’s disease, and major depression. Utilizing this data, machine-learning algorithms were developed to anticipate how variations in DNA sequences could influence gene regulation and contribute to disease etiology.
Future Research Prospects and Aspirations
The research, while illuminating, is far from conclusive in mapping the human brain’s intricacies. In 2022, UC San Diego partnered with the Salk Institute and others to initiate the Center for Multiomic Human Brain Cell Atlas. This center intends to scrutinize cells from numerous human brains to investigate how the brain evolves during developmental phases, across lifespans, and during disease states.
“Expanding our research to include an even greater level of detail and a larger pool of brain samples will bring us incrementally closer to understanding the biological underpinnings of neuropsychiatric disorders and their potential treatment,” Bing Ren stated.
Reference and Acknowledgments
The study’s contributors include numerous professionals from UC San Diego, the Salk Institute for Biological Studies, Karolinska Institute, and Allen Institute of Brain Science, among others. Financial backing for this research was provided by the National Institutes of Health, the National Science Foundation, and various other sources including endowments and corporate gifts.
The research was supported by an array of grants from institutions such as the National Institutes of Health and the National Science Foundation, as well as contributions from Google, Adobe, and Teradata among others.
Frequently Asked Questions (FAQs) about neuropsychiatric disorders
What institutions led the research on brain cell mapping and neuropsychiatric disorders?
The research was spearheaded by the University of California San Diego (UCSD) in collaboration with multiple other institutions, including the Salk Institute for Biological Studies, Karolinska Institute, and Allen Institute of Brain Science.
What is the primary focus of this research?
The primary focus is to map gene regulatory elements across different types of brain cells and establish links between these cell types and common neuropsychiatric disorders such as schizophrenia, bipolar disorder, Alzheimer’s disease, and major depression.
How many human brain cells were analyzed in the study?
The research team analyzed more than 1.1 million brain cells from three different human brains across 42 unique brain regions.
What technology was used to forecast the effects of high-risk gene variants?
Artificial intelligence methodologies were employed to predict the potential contributions of individual high-risk gene variants to neuropsychiatric diseases.
What is the BRAIN Initiative?
The BRAIN Initiative, or Brain Research Through Advancing Innovative Neurotechnologies Initiative, is a program launched by the National Institute of Health in 2014. It aims to revolutionize the understanding of the mammalian brain partly through the development of novel neurotechnologies.
Are there any plans for future research?
Yes, UC San Diego has joined the Salk Institute and others in launching the Center for Multiomic Human Brain Cell Atlas. This center aims to study cells from numerous human brains to understand changes during development, across lifespans, and with disease.
How many different subtypes of brain cells were identified?
The study identified 107 different subtypes of brain cells and related aspects of their molecular biology to a range of neuropsychiatric illnesses.
Who funded the research?
The research was supported by grants from the National Institutes of Health, the National Science Foundation, and other sources including endowments and corporate gifts from companies like Google, Adobe, and Teradata.
The senior author of the study is Bing Ren, Ph.D., a professor at the University of California San Diego School of Medicine.
What are the key takeaways from the study?
The study provides detailed mappings of gene switches in various brain cell types, establishes associations with neuropsychiatric disorders, and uses artificial intelligence to predict the effects of high-risk gene variants.
More about neuropsychiatric disorders
- University of California San Diego Research Publications
- BRAIN Initiative Official Website
- National Institute of Health
- Artificial Intelligence in Medicine
- Science Journal
- Salk Institute for Biological Studies
- Karolinska Institute
- Allen Institute of Brain Science
- National Science Foundation Grants
- DOI: 10.1126/science.adf7044