World news – AU – single cell, « Multi-Omics » analysis reveals a new stage in the formation of immune cells

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Essay 13 November 2020

Australian researchers used the powerful « single cell multiple omics » ???? Techniques for detecting a previously unknown ancestor of T and B lymphocytes (pictured), which are essential components of our immune system. Credit: WEHI, Australia.

Molly Campbell

Science writer

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Karen Steward PhD

Science writer

Over recent years, advances in analytical techniques have allowed scientists to gain insight into cell biology with a whole new level of detail: the single cell level. This approach recognizes cells. Even those who are close to them as part of the same tissues ???? Heterogeneous in nature. Our immune system cells are especially interesting. Although derived from a blood stem cell, each type of immune cell performs an individual specific function. How do these different types of immune cells develop? Led by Dr. Shalin Naik ???? From the Walter Institute and Elisa Hall, a single-cell, multi-omics approach has been adopted to explore this question, with a special focus on the formation of T and B lymphocytes.. Their findings, recently published in Nature Immunology, determine their discovery of a new phase in lymphocyte development, information the researchers say could « inform future studies of the immune system. ». Technology Networks spoke with Naik to find out more about the study findings and why the single-cell and multi-omics approach to studying the immune system helps us capture the « big picture. ». Molly Campbell (MC): For readers who are unfamiliar with the concept, can you tell us about the principle of the polymyotic single cell analysis approach? Shalin Naik (SN): Cells are the building blocks of all of our tissues. Analyzing every cell in an organ is like understanding the stats of an individual player in a soccer match and not just the teams ???? Degrees. Scientists measure many different aspects of cell biology. Proteins, DNA, turn on and off genes, etc.. The more cell features we can measure, the better the picture we can solve. This way we can get close to the true nature of each cell, what it does and how it is relevant to our biology. â € Multi omics ?? An approach that can get as much information as possible for each cell to get the largest possible picture. MC: What is the rationale behind this study, particularly the decision to conduct a single cell analysis in the context of immunology? SN: Our lab studies the immune system using new advanced single cell technologies. We previously found that the immune system’s stem and progenitor cells were very diverse in the types of cells they could make. However, we believed that there were so many « hidden » types of stem and progenitor cells that no one previously had a way to detect them.. If one can understand the diversity of immune cell types, and how they are generated, then we can use this information to generate immune cells for cancer and immunity, but also to stop cancers of an immune cell strain called leukemia. . MC: Can you discuss the methods adopted to achieve multi-omics SN analysis: The method we developed is called single-cell RNA sequencing (scRNA-seq), and it is used to understand gene expression in individual cells. Previously, this was impossible because we were used to sequencing RNA-seq on millions of cells by billions of molecules to get enough signal. Achieving a single-cell signal containing only 20,000 molecules per cell, for large numbers of cells, was a huge challenge. However, we devised a method for analyzing the proteins of cells first (the protein) using flow cytometry and then the RNA molecules of those same cells (transcription). Miniaturization of this technique allowed us to capture each of these « omes » (i. e. multi-omics) for stem and progenitor cells from immune cell lines. Karen Steward (KS): What alerted you to the existence of this unexpected progenitor cell? SN: We previously used stem cell coding and tracking technology to discover that stem cells and progenitor cells were highly heterogeneous in the immune cells they made, but we didn’t know how they achieved it. We needed to uncover cell-to-cell differences in that group to get some clues. We took it upon ourselves to develop a multiple scRNA-omics sequencing technology to get to the core of this answer and find it! MC: I have established a Single Cell Open Research Plan (SCORE). Could you please tell us more about this? SN: After seeing the power of scRNA-seq first hand, we learned this was a technique that would be fast-moving and useful to many, many researchers. Instead of every laboratory reinventing the wheel, we thought creating an integrated team that could cover biology, molecular biology, and bioinformatics analysis, could be quick to embrace new developments in the field so that researchers can focus on what they are doing best ??? MC Biological and Clinical Questions: What are the challenges associated with single cell analysis, and how did you overcome them in this research? SN: People have written entire PhD theses in one small aspect of the many challenges they face with scRNA-seq analyzes.. There are many ways you can look at data, and as a result there is an explosion in the number and types of analyzes to find it. The challenges first and foremost, unlike RNA-seq data on millions of cells, is that data from single cells is very little – ???? Which means there are a lot of 0 in the number of genes ???? It’s a bit like looking at a blurry photo instead of a high-resolution photo. However, there are many ways to extract some information from this data by capturing enough cells, and then using some clever methods to separate the signal from the noise, they say.. KS: How could this new information about the development of T cells and B cells be useful in targeting disorders of the immune system? SN: By understanding the source of T cells and B cells naturally, as we did in this study, we hope to use this information to think about how we can increase the numbers of these types of cells; Either in vaccination, to boost the immune system to aging, or to engineer immune therapies to fight cancer. Some leukemias are « lymphocytes ??? » In nature, which means they have the same origin as their ancestors who make T cells and B cells. Having discovered the first step in lymphatic development, we think this may be the source of such cancers. By understanding the mechanisms of our newly discovered society, we may find clues to the origins of leukemia. Dr. Shaleen Naik was speaking to Molly Campbell and Dr. Karen Steward, Science Writers, Tech Networks.

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World News – AU – Single cell, « Multi-Omics » analysis reveals a new stage in the formation of immune cells

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