The first comprehensive analysis of how the blood and immune systems develop in the prenatal bone marrow was conducted by scientists from the Wellcome Sanger Institute, Newcastle University and their collaborators. Researchers have found that within just a few weeks, many types of blood and immune cells emerge from developing bone marrow, including essential white blood cells that protect against bacteria.
The study, published today (September 29, 2021) in Nature, is part of the Human Cell Atlas (HCA) initiative to map every cell type in the human body, in order to transform our understanding of health, infections and disease. It will be an important benchmark for understanding how the blood and immune systems develop in the bone marrow, and how it can go wrong in disorders such as leukemia, with important implications for diagnosis and treatment.
A previous HCA study described how the human blood and immune system begins to develop in the yolk sac and liver, a process known as hematopoiesis. But until now, it was not known how hematopoiesis proceeds in the bone marrow, which produces blood and immune cells for the rest of an individual’s life.
Although human blood and the immune system generally protect us against infection and disease, the system can go awry and lead to immune deficiencies and cancers such as leukemia.
In this study, researchers at the Wellcome Sanger Institute, the University of Newcastle, the University of Cambridge and the University of Oxford used single-cell RNA technology to analyze samples of marrow tissue. developing bone, in order to identify the types of cells present and the genes of those cells. Express.
The team observed the rapid diversification of blood and immune cells into specialized types, including white blood cells called neutrophils which protect against bacteria. This diversification occurred over six to seven weeks at the start of the second trimester of pregnancy. Compared to the fetal liver, there were a large number of types of B lymphoid cells, which are needed both to help fight infection and to build an effective response to vaccines.
Dr Laura Jardine, first author of the Newcastle University paper, said: “For the first time, we were able to identify all the blood and immune cells in developing bone marrow. It even allowed us to see stromal cells – the environment in which immune cells thrive – which had never been characterized in detail before. This atlas will be a huge resource for researchers.
Professor Muzlifah Haniffa, lead author of the Wellcome Sanger Institute and Newcastle University article, said: “Even though we might have thought that we understand the immune system, it is actually much more complex than we know. had achieved it. Data like this provides the resolution needed to fully understand what happens at the molecular level during development. “
The researchers also studied the bone marrow of Down syndrome, identifying notable differences in gene expression that may help shed light on why people with Down syndrome are more likely to develop immune disorders. and leukemia.
Professor Irene Roberts, lead author of the MRC Molecular Hematology Unit at Oxford University, said: ‘We know that children with Down syndrome have a higher risk of developing leukemia, but we don’t know why. This study characterizes some of the differences in gene expression in their bone marrow, which will allow us to begin to determine if these differences are significant and in what way. We hope this will ultimately help researchers develop better ways to treat, if not prevent, leukemia in these children. “
This research is part of the Atlas of Cells of Human Development (HDCA), which creates an atlas of all cells important for healthy human development. Key to understanding what happens early in development and how it can affect health or lead to disease, HDCA has the potential to lead to transformations in healthcare.
This first detailed map of bone marrow development is another important contribution to the international Human Cell Atlas initiative, which aims to create an openly available human “Google map” of the body for understanding health and disease. It is helping transform our understanding of how the human immune system develops early in life and is likely to lead to new ways of diagnosing and treating patients with immune diseases, including the potential of regenerative medicine. . “
Dr Sarah Teichmann, lead author of the Wellcome Sanger Institute study, co-chair of the Human Cell Atlas Organizing Committee
Wellcome Sanger Institute
Jardine, L., et al. (2021) Blood and immune development in human fetal bone marrow and Down syndrome. Nature. doi.org/10.1038/s41586-021-03929-x.