Scientists have carried out the first comprehensive analysis of how haematopoiesis develops in prenatal bone marrow.
The average human adult produces around one trillion blood cells every day through a continuous process called haematopoiesis. It first occurs during embryonic development and replenishes the blood system. Haematopoiesis also enables the rapid turnover of blood cells in response to infection or disease. However, if haematopoiesis fails, it can lead to immune deficiencies and cancers, such as leukaemia.
Before birth, the process of haematopoiesis begins in the yolk sac and transitions into the liver temporarily before finally becoming established in the bone marrow at around 11 weeks after conception. Very little is known about how haematopoiesis continues in bone marrow after birth, and how foetal bone marrow evolves to meet the needs of a new-born.
Recently, researchers from the Wellcome Sanger Institute, Newcastle University, the University of Cambridge and the University of Oxford carried out the first comprehensive analysis of how haematopoiesis develops in prenatal bone marrow. The study, which used single-cell multi-omics to identify genes expressed and cell types present in developing bone marrow tissue samples, was published in Nature as part of the Human Cell Atlas initiative.
The researchers found that the full haematopoiesis system established itself in foetal bone marrow in the second trimester within a 6-week period. During this time, blood and immune cells rapidly diversified into specialist types, including myeloid cells. These cells are part of the lymphatic system and are important for combatting tissue damage and fighting infection. Interestingly, it was also found that granulocytes and dendritic cell subsets emerged for the first time during this 6-week window. Granulocytes are a type of white blood cell that help the body fight bacterial infections, and dendritic cell subsets are a type of antigen presenting cells.
Additionally, the team studied Down syndrome bone marrow and identified notable differences in gene expression. For example, it was revealed that the development of B lymphocytes and myeloid cells was disrupted. This finding provides a potential explanation for why individuals with Down syndrome are more prone to developing immune disorders and leukaemia.
Exploring how blood and immune systems develop in bone marrow
The results from this study will act as an important reference for understanding how haematopoiesis develops in bone marrow at the beginning of life. Moreover, further research will help to identify what roles failures in blood and immune systems play in disorders such as leukaemia, with important implications for diagnoses and treatments.
For example, survival of a foetus depends on the successful initiation of haematopoiesis in several organs throughout pregnancy. Therefore, a better understanding of this process during development has the potential to inform life-saving transplantation therapies, such as haematopoietic stem cell transplants.
Dr Laura Jardine, an author on the paper from Newcastle University, explained: “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 characterised in detail before. This atlas will be a huge resource for researchers.”
Professor Irene Roberts, another author of the paper from the University of Oxford, said: “We know that children with Down syndrome have a higher risk of developing leukaemia, but we don’t know why. This study characterises 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, leukaemia in these children.”
Image credit: Cancer Treatment Centers of America