Characterization of quiescence and maintenance of skeletal stem/progenitor cells (SSPCs)
Description: Skeletal stem/progenitor cells (SSPCs) are crucial for bone homeostasis and repair. Lifelong bone-forming capacity likely depends on the maintenance of a stem cell pool that consists of slow-cycling or quiescent cells, residing in specialized niches. Although impressive progress has been made in the identification of SSPC populations and their functions, strikingly little is known about the regulatory mechanisms that control the quiescence versus activation of SSPCs in homeostasis, and how these processes are affected by ageing or metabolic disorders. Here, we will test the hypothesis that slow-cycling SSPCs in the bone marrow represent quiescent, functional skeletal stem cells, and characterize their molecular and epigenetic signature. We speculate that disturbances in the stromal-vascular bone marrow compartment, as seen upon ageing and in obesity/diabetes, may disrupt the perivascular niche and thereby impact SSPC quiescence and maintenance of the stem cell pool. Furthermore, based on our preceding findings, we speculate that the small GTPase RhoA may exert a critical role as molecular regulator of SSPC quiescence, stem cell maintenance and controlled activation following injury. Characterizing the regulatory mechanisms controlling SSPC quiescence, including the role of RhoA, and understanding how these are impacted by sex, ageing and disease, will open the door towards modulating SSPC preservation and/or functioning for developing new therapies for bone disorders.
Funder: Fonds Wetenschappelijk Onderzoek
Funding type: fellowship
Funder scheme: FWO junior postdoctoral fellowship
Start date: 2025-10-01
End date: 2028-09-30
Investigators: Seppe Melis, Christa Maes
Institution: FWO
Funded outputs count: 0
Funder award ID: 12AKI26N
OpenAlex ID: G5775514430