In this interview, News-Medical talks to two researchers discussing each of their respective studies that have contributed to the Atlas of Human Cells; Dr. Chenqu Suo of the Wellcome Sanger Institute, co-author of the study ‘Mapping the development human immune system across organs’ and Dr. Cecilia Domínguez Conde of the Wellcome Sanger Institute, co-author of the study ‘Cross-tissue L’ Immune cell analysis reveals tissue-specific characteristics in humans:
Can you please introduce yourself, tell us about your scientific background and what inspired your latest research?
Dr. Chenqu Suo: I am a clinical doctorate. student supervised by Dra. Sarah Teichamnn at the Wellcome Sanger Institute. I graduated with a degree in medicine from Cambridge University in 2014 and started my PhD. in 2019 after working as an intern doctor for five years. With a clinical focus on pediatric rheumatology, I have a keen interest in the development of the human immune system and how research, especially experimental and computational biology techniques, may attempt to unravel the mysteries of this process.
Dra. Cecilia Domínguez Conde: I have been a postdoctoral fellow in the Teichmann Laboratory at the Wellcome Sanger Institute since 2019, where my goal has been to dissect the diversity of human immune cell types into lymphoid and non-lymphoid tissues. Before coming here, I did my PhD. in Immunology at the Molecular Medicine Research Center (CeMM) in Vienna. I dissected the genetic cause of primary undiagnosed molecular immunodeficiencies by exome sequencing. In both areas of research, the power of sequencing technologies and computational approaches has been at the core.
Immune cells can be divided into several groups depending on their function and how they are activated. Could you briefly summarize the different groups of immune cells and their functions, pointing out some previously unexplored populations?
Dr. Chenqu Suo: The immune system is a dynamic network of thousands of different cell types distributed throughout the body. Both atlases focus on tissue immune cells, which play a central role in the human immune system and are often poorly studied compared to those circulating in the blood.
All immune cells develop from the same initial cells before they specialize. Although there are many different types of immune cells, they can be grouped into two main categories. One of them, known as myeloid cells, includes macrophages, monocytes, and dendritic cells. These cells can quickly detect infections. When they encounter a pathogen, they send signals to the rest of the body to begin generating a rapid immune response.
Image credit: Art of Science / Shutterstock.com
The other group, lymphoid cells, includes B cells and T cells that retain the memory of previous infections to allow a rapid response to future exposures. Vaccines are created to train B and T cells to recognize pathogens without exposing the body to other risks of infection.
These studies are part of the International Human Cell Atlas (HCA) consortium. What is a cell atlas and how can it improve our understanding of the immune system and related diseases?
Dr. Cecilia Domínguez Conde: A cellular atlas is a complete map of all the cells that make up a system or organ; for example, both studies looked at the immune system. Both atlases are added to the Human Cell Atlas Initiative, which aims to sequence each cell of the human body and create a complete reference map with the position, function and characteristics of each type of human cell. cell, from development to adulthood.
By creating a complete cell atlas, we can identify new types of cells that were previously unknown and shed light on what happens when something goes wrong and causes disease. Finding out more about the cells that sustain the disease and how they differ from healthy cells can provide insight into treatment and prevention strategies. For example, the findings in our Atlas of Immune Cells have great potential to inform the design of the next generation of vaccination strategies and cell-based therapies.
Regarding the study entitled “Mapping the developing human immune system through the organs”, how did you do your research and what were your main findings?
Dr. Chenqu Suo: In our research, we created an atlas of the developing human immune system across nine organs using spatial transcriptomics and unicellular RNA sequencing to map the exact location of specific cells within tissues. in development. We found different types of immune cells in the early stages of organ development compared to those found later. Some immune cells found in the early stages of the organ suggest that they may help support developing tissues rather than fight pathogens.
We also identified a new type of B cell, B1, and a distinctive subset of T cells known as unconventional T cells. These two new cell types are found more abundantly in the early years of life compared to adults, suggesting that the immune system at this stage is more geared to respond quickly to any pathogenic challenge than the adult immune system.
Regarding the study entitled “Cross-tissue immune cell analysis reveals tissue-specific characteristics in humans,” how did you conduct your research, and what were your main findings?
Dr. Cecilia Domínguez Conde: Using unicellular transcriptomics, we simultaneously analyzed immune cells in 16 tissues from 12 individual adult organ donors. To perform a systematic annotation of cells across tissues, we constructed a reference and a cell-type classifier between tissues, called CellTypist, which can now also be used by the wider scientific community. Through a combination of CellTypist and complementary analysis, we have revealed numerous immune cells in the myeloid and lymphoid lineages and their tissue distribution. For example, in the memory T cell compartment, we find several subtypes of effector and resident memory populations and their TCR clonal characteristics.
How are the results of these studies expected to influence and inform the treatment of the disease?
Dr. Chenqu Suo: Both atlases of immune cells could help identify new therapeutic targets for the development of cell-based drugs and therapies by identifying genes linked to certain diseases, such as certain cancers and autoimmune diseases. An example of this is congenital immunodeficiency, a group of genetic diseases where a child is born without the ability to fight infections. Although some genes have been linked to congenital immunodeficiency, the exact mechanisms and cells involved are still unknown. Our cell atlas can help identify which cells are affected by these genes and at what stage of development they are affected, possibly reporting new therapies in the future.
Image credit: Juan Gaertner / Shutterstock.com
Given the COVID-19 pandemic and COVID-19 vaccines, how could an atlas of immune cells that included different cell types and stages of life help our understanding of efficacy? from the vaccine?
Dr. Cecilia Domínguez Conde: Vaccines work by generating immune responses within the tissues. The creation of an atlas of immune cells that maps the entire immune system may reveal a new understanding of how these cells form and interact. This in-depth reference map of the immune system can serve as a framework for understanding the type of memory T or B cells generated by vaccines, allowing researchers to see which cells and genes would be effective targets.
Within the field of Immunology, what currently unanswered questions would you expect to be answered in the near future?
Dr. Chenqu Suo: Our research has characterized new B and T cell populations, but we need more studies to understand why they are important for proper development. Furthermore, we do not yet know whether these originate from the same progenitors as conventional B and T cells or whether they go through an alternative differentiation pathway. Understanding the origin of these cells will give us more clues as to what environment the immune system needs to grow. This knowledge may develop new ways to grow immune cells in the laboratory that could be used for therapeutic purposes.
What’s next for you and your research?
Dr. Chenqu Suo: I return to clinical practice after my doctorate. and I look forward to doing research along with my daily clinical work. I want to use the same technologies I learned in my PhD. to study pediatric diseases.
Dr. Cecilia Domínguez Conde: I will start my research group at the Genomics Center of the Human Technopoly in Milan to study pediatric immunology and rare diseases that affect immune defense. (
Where can readers find more information?
About Dr. Chenqu Suo
Chenqu is a clinical doctor funded by Wellcome Trust. student supervised by Dra. Sarah Teichmann. Chenqu completed her medical degree from Cambridge University and was a pediatrician in training before joining the laboratory. Her research interests are in human immunology, in particular immune system development, in vitro cell engineering, and implications for understanding and managing disease.
About Dr. Cecilia Domínguez Conde
Cecilia Domínguez Conde is a group leader in the Population and Medical Genomics program at the Human Technopole Genomics Center. After training as a pharmacist at the University of Seville, Cecilia did a doctorate. in Immunology at the Molecular Medicine Research Center (CeMM) in Vienna, where his work focused on dissecting the genetic cause of non-molecularly diagnosed primary immunodeficiencies by exome sequencing. In 2019, Cecilia joined the Wellcome Sanger Institute’s Teichmann Laboratory, where her goal has been to dissect the diversity of human immune cell types into lymphoid and non-lymphoid tissues as part of the Human Cell Atlas initiative. Her research group at HT uses cutting-edge genomic technologies to study the development …