Microglia are key regulators of healthy brain physiology and play an important role in inflammation and disease. Microglial dysfunction has been convincingly linked to a myriad of neurological disorders, making these cells an important target for therapeutic intervention. Microglia are embryonically-derived cells that self-maintain throughout life and exhibit a striking self-renewal capacity. Therefore, these cells form an attractive target for cell therapy, with the rationale of replacing embryonic microglia with gene-engineered counterparts that ameliorate disease. In this project, we aim to lay the foundations for future microglial transplantation therapies. We will rely on cutting-edge technologies and innovative mouse models, to reveal the ability of discrete bone marrow progenitors or iPSC-derived precursors to engraft the brain as microglia-like cells. By using single-cell RNA sequencing and in vivo 2-photon microscopy, we will delineate the cellular and transcriptional dynamics of progenitor-to-microglia differentiation. Furthermore, we will assess the ability of the engrafted microglial populations to self-renew and to compete with embryonic microglia. Finally, we aim to develop an efficient strategy for bone marrow- or iPSC-based microglial replacement that can be translated to human patients. This work holds the potential of introducing a new treatment paradigm for brain disease.
|Effective start/end date||1/01/21 → 31/12/24|
Flemish discipline codes
- Cellular therapy
- Innate immunity
- Neurological and neuromuscular diseases
- single-cell RNA sequencing
- Macrophage replacement therapy