What do healthy bone marrow cells in children look like?

For the first time, researchers have mapped this out.

Scientists at the Princess Máxima Centre examined nearly 91,000 individual bone marrow cells from healthy children.

Their findings show that children’s bone marrow is clearly structured differently from that of adults.

The researchers compiled the data into an overview, an atlas, so that other researchers can also use it.

Bone marrow is found in the centre of your bones.

It produces blood cells such as red blood cells and white blood cells.

In leukaemia and other blood disorders, this process goes wrong; diseased cells develop instead of healthy ones.

Researchers study bone marrow to understand exactly what is going wrong and how children with leukaemia or other blood diseases can best be cured.

Comparing bone marrow cells from healthy and sick children is helpful in this process.

But until now, such data did not exist.

Researchers therefore relied on bone marrow data from adults.

Children’s bone marrow is different

Researchers at the Máxima have now shown that children’s bone marrow works differently and consists of different types of cells, in different proportions.

The data have been compiled into an overview, an atlas, that is now freely available to researchers worldwide.

In this way, this study helps further improve treatments for childhood leukaemia and other blood disorders.

This research project, conducted by the Belderbos group and the Single Cell Genomics Facility, was made possible in part by the Landsteiner Foundation for Blood Transfusion Research and the European Research Council.

The Single Cell Genomics Facility is supported by KiKa (Children Cancer Free Foundation).

Nearly 91,000 cells

The bone marrow cell atlas consists of nearly 91,000 individual bone marrow cells.

These cells come from nine donors aged between two and 32 years, covering multiple developmental stages.

More than 20,000 of these are haematopoietic stem and progenitor cells and mesenchymal stromal cells.

For all cells, both the mRNA expression profile and the surface protein expression were recorded using single-cell technologies.

The ‘architecture’ of the bone marrow was also examined using spatial transcriptomics techniques.

Changes in blood cell formation

Analysis of the data reveals clear age-dependent changes in hematopoiesis, the process of blood cell formation.

In children under ten, the bone marrow is primarily focused on producing B cells.

In teenagers and young adults, the emphasis shifts more toward myeloid and T‑cell production.

In parallel, the bone marrow niche also changes: the cellular and molecular composition of the microenvironment that supports blood formation evolves with age.

The results of this study were published today in Nature Immunology.

Postdoctoral researcher Dr. Evelyn Hanemaaijer, PhD candidate Konradin Müskens, and bioinformatician Ireen Kal share first authorship and carried out the research in the Belderbos group, in close collaboration with the Single Cell Genomics Facility at the Máxima Centre.

Age or cancer related differences

Dr. Mirjam Belderbos, paediatric oncologist and research group leader, led the study together with Dr. Thanasis Margaritis, Single Cell Genomics facility lead.

Belderbos explains: ‘That bone marrow and bone marrow cells differ strongly depending on age is highly relevant.

It shows that comparing cells from sick and healthy children within the same age range is crucial to distinguish cancer‑associated changes from normal age-related differences.’

Margaritis adds: ‘An increasing amount of research is carried out at the single‑cell level.

The insights gained through this work and the atlas will help us, and many others, to further advance research into the development and treatment of childhood leukaemias and other blood‑related diseases.’

Source: Princess Máxima Center for Pediatric Oncology