During these stages, they generated four types of data in a multi-omic approach. retrieved 15 July 2020 All trademarks and rights are owned by their respective owners. We don't put up a paywall – we believe in free access to information of public interest.
The study also shows that a multi-omic approach in a hypothesis-free study can generate interesting biological insights that are not obvious if only one process in the cell is observed. As a result, nearly eight percent of the DNA that lines our chromosomes includes remnants of these genes. The researchers were also … “It shows that you don’t always need to have a clear biological question to start with. The researchers discovered that, once the neuronal cells reached the final stage in which they couldn’t divide any further, Sox2 changed its interaction network and took on completely different tasks. For every cell in the body there comes a time when it must decide what it wants to do for the rest of its life. from https://phys.org/news/2020-07-junk-dna-free-stem-cells.html. In mature neuronal cells, Sox2 interacts with a chromatin remodelling factor called Atrx. No effective treatments are available for such motor neuron diseases or spinal cord injuries. For every cell in the body there comes a time when it must decide what it wants to do for the rest of its life. DOI: 10.1073/pnas.2002427117, Citation: Every molecular layer seemed to dominate a different step of the differentiation process. These so-called induced motor neurons possess characteristics of normally developed motor neurons, including distinctive electrophysiological responses and the ability to engraft into the developing spinal cord. “By using a multi-omic approach during four stages of the complex process of cellular differentiation, we got more than just a mere sum of these layers,” says Daria Bunina, an EMBL Interdisciplinary Postdoc (EIPOD) in the Zaugg and Noh groups at EMBL Heidelberg, who led the collaborative study between the two groups and the group of EMBL alumnus Jeroen Krijgsveld at DKFZ.
Judith regularly organises conferences about challenges and opportunities of multi-omics data integration and knows that many scientists in different fields struggle with the interpretation of their multidimensional data. Now, in study published in Nature, the researchers have found that transplanted embryonic nerve cells properly differentiated into pyramidal cells, forming normal synaptic connections, responding to visual stimuli, and carrying out the tasks performed by the damaged cells (videos here). During normal embryonic development, the fate of stem cells is controlled by transcription factors, proteins that act in the cell nucleus to regulate gene function. It has only recently become possible to grow motor neurons from human embryonic stem cells, Dr. Kerr adds. A multi-omic approach is best described as the combination of several omics disciplines. Stem cell-derived motor neurons are a promising research tool for modeling disease and injury and developing therapeutic approaches. Credit: Nath lab, NIH/NINDS. NIH scientists showed how ancient retroviral genes, or “junk DNA”, may play a role in helping stem cells decide to become neurons. Scientists at EMBL Heidelberg have investigated stem cells – the earliest type of cells in an organism, which can divide indefinitely and change into all other types of cells – and how they change, or differentiate, to become neurons. In this study, led by Tongguang (David) Wang, M.D., Ph.D., staff scientist at NINDS, the team showed that deactivation of the gene may free stem cells to become neurons. The researchers sped up this process by turning off HERV-K, HML-2 genes in the stem cells or by treating the cells with antibodies against the HML-2 protein. More information: Wang, T. et al., Regulation of stem cell function and neuronal differentiation by HERV-K via mTOR pathway, PNAS (2020). Stem-cell-derived neurons mirror connections of damaged neurons. Over the course of evolution, the human genome has absorbed thousands of human endogenous retrovirus genes. Muscle movements, such as breathing, walking, speaking, and fine motor skills, are controlled by the activity of motor neurons. Your email address will not be published. The other molecular layers they examined were gene expression, protein expression, and the activity of transcription factors – proteins that bind to specific DNA sites and regulate the expression of genes. Changing their interaction partner to another transcription factor can lead to them having entirely different functions, which has recently been studied by the Zaugg group. “From this, we can conclude that Sox2’s switching of its interaction partners allows it to regulate a completely different set of genes in neurons,” says Daria. EMBL scientists investigate at four different molecular levels how embryonic stem cells become mature nerve cells. This method can be used to produce specific types of motor neurons from stem cells to study how these cells work and what happens when they deteriorate. Turning off ‘junk DNA’ may free stem cells to become neurons (2020, July 13) Finally, the team discovered that interactions on the stem cell surfaces between HML-2 and another immune cell protein called CD98HC may restrain differentiation by triggering internal chemical reactions that are known to control cell growth and tumors. Scientists at EMBL Heidelberg have investigated stem cells – the earliest type of cells in an organism, which can divide indefinitely and change into all other types of cells – and how they change, or differentiate, to become neurons.
In contrast, they delayed neural differentiation by artificially overloading the cells with the HML-2 genes. The study provides a valuable resource for other scientists, because it generated various large omics datasets. “There is an exponential increase in multi-omics studies, but when you look at them and check how many actually gain some sort of mechanistic insight, it’s a small percentage that isn’t increasing much yet,” she says. They then saw that the expression of nearby genes decreased. Well, unlike many news organisations, we have no sponsors, no corporate or ideological interests. “This study clearly shows the right direction to go in when you’re confronted with large, entangled datasets,” she says. But the detailed mechanisms by which transcription factors regulate gene expression and specify cell identity remain largely enigmatic. These can be used to investigate specific genes or proteins. Citation: Turning off ‘junk DNA’ may free stem cells to become neurons … The forced expression of transcription factor combinations known as programming modules has been used to produce specific types of neurons in the lab. “We could study the relationships between different layers during the same stage of differentiation, as well as the relationship between the four stages of differentiation as a whole.
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During normal embryonic development, the fate of stem cells is controlled by transcription factors, proteins that act in the cell nucleus to regulate gene function. Copyright © document.write(new Date().getFullYear()); Society for Neuroscience, 1121 14th Street NW, Suite 1010, Washington, DC 20005, Best Practices for Mentoring Relationships, Foundations of Rigorous Neuroscience Research, Increasing Women in Neuroscience Toolkits, Promoting Awareness and Knowledge to Enhance Scientific Rigor in Neuroscience, Stem Cells and Reprogramming Methods for Neuroscience: An SfN Training Series, Stem Cells As a Tool for Studying the Developmental Regulation of Gene Expression, Layer 5 of Neocortex Gives Rise to Diverse Corticofugal Pathways, How SfN's Founding Hopes Still Fuel Goals for the Next 50 Years. Stem cells could, for example, replace nerve cells after a stroke. Material below is adapted from the SfN Short Course Stem Cells As a Tool for Studying the Developmental Regulation of Gene Expression, by Hynek Wichterle, PhD, et al. Fellow EMBL group leader Kyung-Min Noh explains that multi-omic approaches are often attempted, but it is very difficult to obtain a meaningful outcome from the large amount of data they generate.
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