Study sheds light on blood and immune systems development in prenatal bone marrow

Researchers at the Wellcome Sanger Institute, Newcastle University, and their associates carried out the first extensive investigation of the formation of the blood and immune systems in the prenatal bone marrow.

Image Credit: Novopath, Newcastle Upon Tyne NHS Trust.

The scientists discovered that within a few weeks, many blood and immune cell types arise from the developing bone marrow, including major white blood cells that safeguard against bacteria.

The research is part of the Human Cell Atlas (HCA), an initiative to sketch all cell types in humans, to diversify the knowledge of health, infection, and disease. This would be a vital reference to know the development of the blood and immune systems in the bone marrow.

Moreover, it is also possible to know how this slips off in disorders like leukemia, with significant effects for diagnoses and treatments. The study was published on September 29^th, 2021, in the Nature journal.

An earlier HCA research demonstrated the development of human blood and immune systems in the yolk sac and liver—a process named hematopoiesis. However, to date, the continuation of hematopoiesis in the bone marrow was unknown. Bone marrow produces blood and immune cells throughout the lifespan of an individual.

Even though the human blood and immune systems normally safeguard an individual from disease and infection, the system might fail, leading to immune deficiencies and cancers like leukemia.

In the current research, scientists from the Wellcome Sanger Institute, Newcastle University, the University of Cambridge, and the University of Oxford employed single-cell RNA technology to examine developing bone marrow tissue samples, to pinpoint the cell types and the genes the cells express.

The researchers found that the blood and immune cells quickly diversify into specialist types, including white blood cells known as neutrophils that safeguard against bacteria. This diversification takes place from six to seven weeks early in the second trimester of pregnancy. In contrast to the fetal liver, there was a huge number of B-lymphoid cell types, which are required to fight infection and elicit an effective response to vaccines.

For the first time, we were able to identify all the blood and immune cells in developing bone marrow. This even allowed us to see the stromal cells—the environment that the immune cells develop in—which never been characterized in detail before. This atlas will be a huge resource for researchers.”

Dr Laura Jardine, Study First Author, Newcastle University

Muzlifah Haniffa, the senior author of the study, states, “However much we may have thought that we understood the immune system, it is far more complex than we had realized. Data like this provides the resolution needed to properly understand what is happening at a molecular level during development.” Haniffa is a professor at Wellcome Sanger Institute and Newcastle University.

The scientists also examined Down syndrome bone marrow, pinpointing noteworthy differences in gene expression that might help to provide insights on why people with Down syndrome develop immune disorders and leukemia.

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 start figuring out whether these differences are significant and in what way. We hope this will ultimately help researchers develop better ways of treating, or even preventing, leukemia in these children.”

Irene Roberts, Study Senior Author and Professor, MRC Molecular Haematology Unit, University of Oxford

The study is part of the Human Developmental Cell Atlas (HDCA), which produces an atlas of all cells that are vital for healthy human development. The key is to know the happenings in early development and how this affects health or results in diseases. The HDCA leads to transformations in healthcare.

This first detailed map of developing bone marrow is another important contribution to the international Human Cell Atlas initiative, which aims to create an openly available human ‘Google map’ of the body to understand health and disease.”

Dr Sarah Teichmann, Study Senior Author, Wellcome Sanger Institute

Dr Teichmann, who is also the co-chair of the Human Cell Atlas Organising Committee, further adds, “It is helping to transform our understanding of how the human immune system develops in early life and is likely to lead to new ways of diagnosing and treating patients with immune diseases, including the potential for regenerative medicine.”