Investigating the bone marrow niche dynamics during clonal haematopoiesis

This is a summer student position supervised by Despoina Papazoglou in Dominique Bonnet's lab.

Introduction to the science

In the Bonnet lab, we study how human blood stem cells (called haematopoietic stem cells, or HSCs) work in both healthy people and in blood cancers such as acute myeloid leukaemia. We don’t just focus on the stem cells themselves — we also look at the support cells around them, known as stromal cells. These stromal cells reside in the bone marrow “niche,” the environment that surrounds and influences HSCs. By understanding both the stem cells and their supporting environment, we aim to learn how normal blood formation works and how it goes wrong in cancer.

About the project

During my postdoctoral research, I am investigating a biological process known as clonal haematopoiesis (CH). In CH, a subset of haematopoietic stem cells (HSCs) acquires somatic mutations that give these cells a growth advantage over non-mutated (wild-type) HSCs. CH is associated with an increased risk of developing haematological malignancies and other conditions, such as cardiovascular disease. However, many individuals with CH never develop these disorders, and the reasons for these different outcomes remain unclear.

A major unanswered question is how mutant HSCs expand and, importantly, how their presence influences other cell types within the bone marrow. My work focuses on mesenchymal stromal cells (MSCs), a key stromal population that plays essential roles in supporting normal haematopoiesis.

To study these interactions, we have established a three-dimensional humanised scaffold model that enables investigation of human CH in vivo. The scaffolds are seeded with HSCs and MSCs and then implanted into mice. After three months, we retrieve the scaffolds and analyse them using flow cytometry, single-cell RNA sequencing, and immunofluorescent staining. Although we have preliminary data on the cell populations present, we still lack a detailed understanding of the architecture of these niches and the spatial organisation of the various cell types.

The summer student will contribute to this work by developing multiplex imaging approaches, alongside learning cell culture and flow cytometry. The overall aim of their project will be to characterise the presence and spatial distribution of multiple stromal cell types within our human bone marrow model and to compare these features under healthy versus CH/mutant conditions.

Candidate background