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A new study published this week in Nature, provides the most detailed analysis so far of the prenatal development of blood and immune cells in the bone marrow.

A longitudinal section of fetal femur with multiplex immunofluorescent staining, showing CD34 in red and VEGFR2 in green.
A longitudinal section of fetal femur with multiplex immunofluorescent staining, showing CD34 in red and VEGFR2 in green.

Throughout development our cells are in continual need of oxygen and nutrients and need to build the components of a sophisticated immune system ready to protect us from the moment of birth. The cells that do this are all provided by the blood and immune system. The emergence of these systems happens in multiple phases across several organs in a process known as haematopoiesis. Early in development, production of both red blood cells and immune cells begins in the yolk sac, before transitioning to the fetal liver, and then to the fetal bone marrow where it begins a life-long role.

In the study, which is part of the Human Cell Atlas (HCA) initiative to provide comprehensive reference maps of every cell type in the human body, researchers from a range of institutions including Professor Irene Roberts and Associate Professor Andi Roy both of the MRC Molecular Haematology Unit, the MRC Weatherall Institute of Molecular Medicine and the Department of Paediatrics at the University of Oxford, pinpoint a specific 6-7 week window in the second trimester, during which the full range of blood and immune cells are established in the bone marrow.

This data will be a valuable reference for researchers exploring the nature of the blood and immune system, especially where changes in those processes lead to diseases such as cancers. As part of the project researchers also studied Down syndrome bone marrow. Children with Down syndrome are known to be at increased risk of childhood leukaemias as well as immune deficiency and autoimmune diseases, making understanding development of the immune and blood systems incredibly important.

Professor Irene Roberts, a senior author of the paper 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.”

“This project allowed us to study how haematopoiesis is established before birth in the bone marrow, the site for subsequent lifelong blood cell production. More importantly we show the utility of datasets such as this in understanding the effects on human health when these processes are perturbed”  said Professor Andi Roy a senior co-author of the paper.

This research was funded by Wellcome, the Medical Research Council (MRC) and funding to individual authors. Both Professor Irene Roberts and Professor Andi Roy’s work is funded by the NIHR Oxford Biomedical Research Centre.

Read the full press release from the Wellcome Trust Sanger Institute here.

Read the full paper here