Stem Cells and Organoid Biology
Title of project
The interplay between senescence and stem cells in tissue regeneration
A 4-year PhD student position in the interdisciplinary area of regenerative medicine. The project will focus on investigating through which mechanisms senescent cells induce pluripotency (I), how such a persistent lock of stemness can impair tissue regeneration (II) and how this may affect tumor therapy resistance (III).
You will be hosted by the Department of Pathobiology, Faculty of Veterinary Medicine of Utrecht University (UU) and the Center of Molecular Medicine of University Medical Center Utrecht (UMCU). This project is jointly supervised by Alain de Bruin, UU and Peter de Keizer, UMCU.
Tissue regeneration relies on faithful differentiation of stem cells. However during aging the regenerative capacity of tissues is impaired and the inhibitory mechanism on tissue stem cells are largely unknown When healthy cells are irreparably damaged, they can enter a state called senescence (White et al. Nat Commun 2015). Senescent cells continuously secrete a range of molecules that alter their local milieu, the Senescence Associated Secretory Phenotype (SASP). As such, senescent cells have been found to be directly causative for tissue aging and loss of homeostasis (Baar et al. Cell 2017). We have observed that senescent cells are often flanked by cells that are in a state of pluripotency. Moreover, we have found that SASP factors can trigger stemness in healthy and cancer cells. In cancer cells, this makes them more resistant to treatment. In healthy cells, we hypothesize that SASP factors prevent differentiation of tissue stem cells and thereby impair tissue rejuvenation (de Keizer Trend Mol Med 2017) Together, this calls for investigation on how senescent and stem cells interact and how mitigation of their negative interplay may improve tissue regeneration during aging and affect migration of therapy-resistant cancer.
Contact person & more information
Prof. dr. Alain de Bruin, Professor in Pathobiology, Faculty of Veterinary Medicine
Dr. Peter de Keizer, Assistant professor “Senescence in Cancer and Aging, Center for Molecular Medicine
This project is part of RESCUE, a multidisciplinary, intersectoral and interdisciplinary PhD training programme in Regenerative Medicine and Stem Cells organised by UMC Utrecht (coordinator) and Utrecht University. RESCUE is partly funded by the European Commission under Horizon 2020's Marie Skłodowska-Curie Actions COFUND scheme. There are specific requirements with regards to English language and mobility for candidates who would like to take part in this programme. More information