#29 Stem Cell Models, Complex Cuttlefish Camouflage and a New Universal RNA Tool...
How stem cell models are helping to unravel psychiatric disorders, cuttlefish camouflage is more complex than we may have thought and a new single cell RNA tool that could become a universal tool...
🧠Stem Cells and Psychiatry
Stem cell model unravelling psychiatric disorders…
A research team based at the Icahn School of Medicine at Mount Sinai have applied a new stem cell model to help in the mapping of disease risk variants in human neurons. In doing so the team hopes to be able to provide insights into some of the biological mechanisms that underlie neuropsychiatric disorders such as autism. Due to the proliferation and differentiation capacity of human stem cells scientists can use them as more clinically relevant models to study diseases.
The in vitro model aims to show the disease mechanisms that are involved in genome wide association studies (GWAS) that characterise different risk alleles for psychiatric disorders. With numerous long term applications, this research could lead to improved diagnostics for the detection of disorders before symptoms begin to show themselves.
The research team focuses on mapping cis-regulatory elements in human neurons. This was due to a few reasons, such as the fact that previous genetic studies have revealed a significant enrichment of common variants in the cis regulatory elements including those associated with autism, schizophrenia and bipolar disorder. Cis regulatory elements are simply regions of non coding DNA which regulate the transcription of neighbouring genes. The term includes promoters and enhancers and due to their regulatory role in gene expression they are vital components of the regulatory network.
Nan Yang, PhD and Assistant Professor of Neuroscience at the school as well as senior author of the study stated that "While common risk variants can shed light on the underlying molecular mechanism, identifying causal variants remains challenging for scientists,". They went on to say that “because cis-regulatory elements, particularly the enhancers, vary across cell types and activity states. Typically, researchers can only use post-mortem brain samples where the neurons are no longer active. As a result, they are likely to miss enhancers that only respond to stimulation. Our approach is to map cis-regulatory elements in human neurons derived from pluripotent stem cells. That allows us to replicate neurons in the human brain that can be affected by different types of neuropsychiatric disease, and conduct mechanistic studies of human genetic variants that are inaccessible from other types of human samples."
In recent years the GWAS technology has identified hundreds of associated gene regions. In doing so the team has developed stem cell models to help resolve the impact. Decoding and transferring highly complex genetic information should allow the team to posses medically actionable information. Resultantly they hope to improve diagnostic capabilities, predicting clinical trajectories and identifying presymptomatic points of therapeutic intervention.
By characterising cell type specific and activity-regulated gene expression patterns in human cell-derived neurons the team hope to benefit the research community and help to further elucidate some of the molecular mechanisms of disease across the genome. This could lead to the development of biomarkers that may detect neuropsychiatric disorders years before they manifest themselves.
Cuttlefish camouflage more complex than thought…
The European cuttlefish Sepia officinalis may have two neural systems that are responsible for processing specific visual features from the cuttlefishes environment to create body patterns used to camouflage itself on the sea floor.
This is more complex than previous research suggested, by which cuttlefish had simplex cognitive process, adopting just one of three major types of body patterns to visually merge with its background. The animal actually possesses roughly 30 different pattern components to bring about their famous “camouflage”.
Similar to other cephalopods, cuttlefish blend with their environment though pigments in the skin. Cuttlefish camouflage due to the direct action of their brain onto chromatophores (specialised skin cells). These act as pixels that together, portray changing colour on the skin of the organism. The study explored whether the cuttlefish uses a cognitive process triggered by specific visual features in the environment which warrant the number of body pattern components used.
15 European cuttlefish were independently acclimated to a small water tank in which they were exposed to either a plain grey background or a detailed and patterned background. The camouflage responses were photographed and analysed to see which of the 30 body pattern components appeared activated across the sample of cuttlefish.
The analysis of these photos and their results included statistical analysis through the use of principal component analysis (PCA). This searches for clusters of responses in the observed data and attempts to largely explain it with a reduced set of key characteristics. The results of this found that a few key characteristics did not explain most of the variability in the experimental data. The test should have explained the majority of variability should the cuttlefish have employed a cognitive system which only expressed three body patterns. The study was more in line with a system where the full range of animals body pattern components could be activated, however selectively and in response to the patterned water feature they were exposed to.
Whilst preliminary, the study suggests that the cuttlefish do employ a cognitive system to process their environment, which is used in combination with a system that response to the visual background overall. In addition, it is implemented in a more hierarchal fashion to allow the animal to create the myriad camouflages used on the seafloor.
"The cuttlefish provides a fascinating window into perceptual processing of such an alien species by expressing its perception of the surroundings on the dynamic canvas of its skin surface” said Christopher Tyler, Professor of visual science at City, University of London.
🔨New Universal Tool?
Single-cell RNA sequencing to become universal tool…
A new single cell RNA sequencing protocol allows the detection of a significantly higher number of genes per cell, than any existing method. Furthermore, it is less expensive and more sensitive…
Single-cell RNA-sequencing (scRNA-seq) shows which genes are turned on, and what their level of transcription is. Due to the in depth nature of this method their are a number of applications in disease and disease biology. scRNA-seq is becoming widely used across disciplines such as developmental biology, immunology, cardiovascular research and infectious diseases. The applications of this method already reach far beyond this with single cell sequencing widely used in the analysis of de novo germline mutations and somatic mutations in normal and diseased cells, such as cancer cells.
The developed protocol can be used to study any disease model requiring the analysis of rare cell populations, at high resolution.
"Our modular FLASH-seq protocol provides a snapshot of the cell transcriptome at an unprecedented resolution. The method can be miniaturized, automated and adapted to different needs. It helps to define which gene isoforms are present in health and disease. It also provides a much deeper picture of the gene expression, especially after perturbation due to disease, developmental defects or external agents. Moreover, it is easy to set up in the lab, 50% faster and cheaper than similar existing protocols and enables the study of molecular mechanisms of disease beyond the scope of current single-cell sequencing tools” said Simone Picelli, Head of the IOB single-cell genomics platform and lead author.
This method can generate sequence ready libraries in just half a day. Researchers at IOB therefore believe that FLASH-seq has the potential to become the tool of choice when looking for efficient and automation friendly full-length RNA sequencing.
🦠 Disease and Illness
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🧠Stem Cells and Psychiatry
Sanchez-Priego, C., Hu, R., Boshans, L., Lalli, M., Janas, J., Williams, S., Dong, Z. and Yang, N., 2022. Mapping cis-regulatory elements in human neurons links psychiatric disease heritability and activity-regulated transcriptional programs. Cell Reports, 39(9), p.110877.
Osorio, D., Ménager, F., Tyler, C. and Darmaillacq, A., 2022. Multi-level control of adaptive camouflage by European cuttlefish. Current Biology,.
More Information - https://www.city.ac.uk/news-and-events/news/2022/05/cuttlefish-camouflage-may-more-complex-previously-thought#:~:text=Study%20suggests%20that%20European%20cuttlefish,camouflage%20themselves%20within%20underwater%20surroundings.
🔨New Universal Tool?
Hahaut, V., Pavlinic, D., Carbone, W., Schuierer, S., Balmer, P., Quinodoz, M., Renner, M., Roma, G., Cowan, C. and Picelli, S., 2022. Fast and highly sensitive full-length single-cell RNA sequencing using FLASH-seq. Nature Biotechnology,.