New Insights into Mental Health through NeuroPainting
Research using NeuroPainting uncovers links between genetics and brain cell behavior.
Matthew Tegtmeyer, Dhara Liyanage, Yu Han, Kathryn B. Hebert, Ruifan Pei, Gregory P. Way, Pearl V. Ryder, Derek Hawes, Callum Tromans-Coia, Beth A. Cimini, Anne E. Carpenter, Shantanu Singh, Ralda Nehme
― 7 min read
Table of Contents
- The Importance of Researching Genetic Factors
- New Ways to Study Brain Cells
- The Power of NeuroPainting
- Getting to Know NeuroPainting
- Finding Differences in Cell Types
- The Impact of the 22q11.2 Deletion
- Looking Deeper into Astrocytes
- Discovering Links Between Genes and Cell Features
- Wrapping Up the Findings
- What’s Next for NeuroPainting?
- Original Source
- Reference Links
Mental health issues are a big problem worldwide. People who suffer from these conditions often deal with tough symptoms like wild mood swings, seeing things that aren’t there, and a higher chance of misusing drugs or thinking about suicide. These struggles can lead to serious problems for both individuals and society, including job loss, homelessness, and imprisonment.
For a long time, the main treatments for mental health issues have been talk therapy and medications. But, these methods don’t work for everyone. More than half of people fighting with conditions like schizophrenia and bipolar disorder still find it hard to function in their daily lives. This shows there is a big gap in our knowledge about what causes these disorders, and progress in treatment development has been slow because of how complicated these issues are. Many factors, both genetic and environmental, play a role in mental illnesses.
The Importance of Researching Genetic Factors
One area of focus is a specific genetic change found on chromosome 22q, called the 22q11.2 microdeletion. This deletion is a well-known change linked to a condition called DiGeorge Syndrome, which can affect many different systems in the body, including the brain. This genetic change is also closely related to schizophrenia. While scientists have linked other health problems to this deletion, the brain-related impacts are still not well understood.
On chromosome 22q, there are also many common genetic variations that can influence health traits, including those related to the 22q11.2 deletion. Because the effects of this deletion can vary widely among individuals, it’s crucial to have thorough research methods to uncover how this genetic change works at a biological level. By doing so, researchers hope to identify pathways affected by this deletion and understand how it impacts different types of cells, which could lead to better treatments for schizophrenia and similar disorders.
New Ways to Study Brain Cells
One promising method to study brain-related issues is called Cell Painting. This approach allows scientists to look at how cells look under a microscope without needing to focus on any one specific part or type of cell beforehand, which can avoid some common errors. This technique has already been used in various studies to understand how genes work, how different types of cells behave, and to create helpful guides for other researchers.
Studying cell shapes and features can offer many benefits over methods that only look at gene activity levels. While gene activity gives hints about how much protein a cell might make, changes in cell shape can provide a clearer picture of how cells actually function.
Recent studies have shown that researchers can find disease-related changes directly from patient samples without guessing what those changes might look like. For instance, scientists have examined skin cells from individuals with Parkinson’s disease and noticed distinct changes in cell shape and structure compared to healthy people.
The Power of NeuroPainting
To take this a step further, a new method called NeuroPainting was created. This method is based on Cell Painting and allows researchers to study specific brain cells derived from human induced pluripotent stem cells (iPSCs). This means scientists can examine many different cell types at the same time and potentially capture variations that exist among different individuals.
Researchers used NeuroPainting to find cellular characteristics tied to the 22q11.2 deletion. They could see differences between various cell types, highlighting how NeuroPainting can help understand complex biological questions related to mental health.
Getting to Know NeuroPainting
NeuroPainting works by using special dyes that stain different parts of the cells, making them easier to see under a microscope. Researchers gathered samples from numerous iPSC lines, some with the 22q11.2 deletion and some without. All samples were treated and examined under the same conditions, which helped reduce errors and ensure reliable results.
The scientists created a detailed plan to analyze the shapes and traits of the cells. They measured thousands of characteristics, such as size, shape, and texture, to create a comprehensive profile for each cell type. By doing so, they could pinpoint distinct traits that separate different types of cells.
Finding Differences in Cell Types
When researchers looked at the data, they found significant differences in the shapes and features of the cells based on their type and genetic background. They trained a machine learning model to classify these cell types by their characteristics, achieving high accuracy in identifying different cell types.
The results revealed specific traits that distinguished each type of brain cell. This ability to classify cell types using NeuroPainting could help researchers study how genetic changes impact cells in mixed groups. Moreover, this tool could shed light on how drug treatments or genetic mutations might change cell behavior over time.
The Impact of the 22q11.2 Deletion
The next step for researchers was to see how the 22q11.2 deletion affected the brain cells. They found that this deletion caused noticeable changes in Cell Structure, indicating that the deletion had a significant impact on cell shapes.
By applying NeuroPainting to cells from individuals with the 22q11.2 deletion, scientists could differentiate them from healthy controls. This finding opens up new possibilities for using NeuroPainting to identify potential drug targets related to this genetic change.
Astrocytes
Looking Deeper intoAstrocytes are a type of brain cell that play a vital role in supporting neurons. Researchers noticed that the 22q11.2 deletion led to many differences in astrocyte traits. This raises questions about how changes in astrocytes might relate to psychological conditions, as recent studies have linked astrocytes to various mental health issues.
To further investigate, scientists collected and analyzed cell data to see how gene expression patterns changed in astrocytes with the deletion. By comparing the cells, they were able to link specific changes in gene activity to the observable changes in cell shape.
Discovering Links Between Genes and Cell Features
Through careful analysis, researchers identified strong connections between the altered Gene Expressions in astrocytes and changes in their morphology. They found that many genes affected by the deletion corresponded to specific morphological traits in the cells.
The researchers highlighted several key findings, suggesting that the deletion leads to disruptions in cell adhesion and could make astrocytes more prone to cell death. This could explain some of the broader effects linked to the 22q11.2 deletion in mental health.
Wrapping Up the Findings
In summary, NeuroPainting is a powerful tool that helps researchers identify unique features of brain cells and understand how genetic changes impact their behavior. By focusing on specific genetic changes like the 22q11.2 deletion, scientists can gain insights into the biological underpinnings of various mental health conditions.
NeuroPainting not only facilitates the identification of potential targets for drug development but also helps create a deeper understanding of how brain cells function. This work paves the way for future research to explore even more complex cellular behaviors and potential therapeutic strategies for mental health disorders.
What’s Next for NeuroPainting?
While the findings so far are promising, researchers recognize there’s still much more to explore. Currently, they face challenges studying neuron cells, which are more complex in shape and behavior compared to other cell types. Future studies will ideally include larger sample sizes to address variability in data and improve accuracy.
Moreover, incorporating NeuroPainting with additional techniques that focus on synaptic functions could provide even deeper insights into brain cell connections. Overall, the hope is that this innovative approach will lead to new ways of thinking about treatment and understanding mental health disorders.
In conclusion, NeuroPainting has opened doors to new methodologies in studying the brain and offers the potential for better insights into the pathways that lead to mental health disorders. By connecting genetic changes with observable cell behaviors, researchers can better understand the underlying mechanisms of psychiatric conditions, ultimately leading to more effective therapies.
Title: Combining NeuroPainting with transcriptomics reveals cell-type-specific morphological and molecular signatures of the 22q11.2 deletion
Abstract: Neuropsychiatric conditions pose substantial challenges for therapeutic development due to their complex and poorly understood underlying mechanisms. High-throughput, unbiased phenotypic assays present a promising path for advancing therapeutic discovery, especially within disease-relevant neural tissues. Here, we introduce NeuroPainting, a novel adaptation of the Cell Painting assay, optimized for high-dimensional morphological phenotyping of neural cell types, including neurons, neuronal progenitor cells, and astrocytes derived from human stem cells. Using NeuroPainting, we quantified cell structure and organelle behavior across various brain cell types, creating a public dataset of over 4,000 cellular traits. This extensive dataset not only sets a new benchmark for phenotypic screening in neuropsychiatric research but also serves as a gold standard for the research community, enabling comparisons and validation of results. We then applied NeuroPainting to identify morphological signatures associated with the 22q11.2 deletion, a major genetic risk factor for schizophrenia. We observed profound cell-type-specific effects of the 22q11.2 deletion, with significant alterations in mitochondrial structure, endoplasmic reticulum organization, and cytoskeletal dynamics, particularly in astrocytes. Transcriptomic analysis revealed reduced expression of cell adhesion genes in 22q11.2 deletion astrocytes, consistent with recent post-mortem findings. Integrating the RNA sequencing data and morphological profiles uncovered a novel biological link between altered expression of specific cell adhesion molecules and observed changes in mitochondrial morphology in 22q11.2 deletion astrocytes. These findings underscore the power of combined phenomic and transcriptomic analyses to reveal mechanistic insights associated with human genetic variants of neuropsychiatric conditions.
Authors: Matthew Tegtmeyer, Dhara Liyanage, Yu Han, Kathryn B. Hebert, Ruifan Pei, Gregory P. Way, Pearl V. Ryder, Derek Hawes, Callum Tromans-Coia, Beth A. Cimini, Anne E. Carpenter, Shantanu Singh, Ralda Nehme
Last Update: 2024-11-17 00:00:00
Language: English
Source URL: https://www.biorxiv.org/content/10.1101/2024.11.16.623947
Source PDF: https://www.biorxiv.org/content/10.1101/2024.11.16.623947.full.pdf
Licence: https://creativecommons.org/licenses/by/4.0/
Changes: This summary was created with assistance from AI and may have inaccuracies. For accurate information, please refer to the original source documents linked here.
Thank you to biorxiv for use of its open access interoperability.