Our research focuses on understanding genome instability in human pluripotent cells, its mechanims of origin and its consequences. We work on two types of pluripotent cells: early human embryonic cells and human pluripotent stem cells (hPSC).
Early studies using FISH on human preimplantation embryos revealed already in the past decade that the early stages of human development are prone to aneuploidies. Over the past years, we have been involved in the development of the first methods for the study of the full chromosomal content of single cells, and have carried out comprehensive studies of the genetic content of human embryos at the cleavage-stage of development. Next to our interest in characterizing the levels of abnormality in these embryos, we are working on the better understanding of the mechanisms behind, with a focus on cell cycle abnormalities. More recently, our interest has turned to the integrity of the mitochondrial genome in these key stages of human life.
Human embryonic stem cells (hESC), derived from preimplantation embryos, and human induced pluripotent stem cells (hiPSC), obtained by the reprogramming of somatic cells, hold a great promise in the field of regenerative medicine because of their potential to develop into any cell type of the adult individual. Intensive research over the past 15 years has yielded numerous protocols for the differentiation of hPSC into nummerous cell types, and the first steps towards the clinic have been taken. Currently, one of the key issues in this regard is the genomic stability of hESC during culture. We and others have shown that hESC are prone to chromosomal abnormalities, including aneuploidies, fragile site expression and small duplications with a hotspot at 20q21.11. This genomic instability strongly reminds of the behaviour of cancer cells, and is of great concern for the use of hEPC for therapeutic purposes or as reliable research models. In our lab we study the origin, extent and consequences of this genetic instability.
FILIPPO ZAMBELLI. “Mitochondrial DNA mutations in pluripotent cells”. 29/03/2018. Supervisors: Prof. Spits, Dr. Gianaroli, Prof. Barboni. Joint PhD with the University of Teramo.
ANNA SERIOLA PETIT. “Pluripotent stem cells as research models: the examples of trinuceotide repeat instability and X-chromosome inactivation”. 21/09/2015. Supervisors: Prof. Spits, Prof. Santaló. Joint PhD with the Universitat Autonoma de Barcelona.
AFRODITI MERTZANIDOU. “Chromosomal abnormalities in human preimplantation development”. 29/04/2015. Supervisors: Prof. Spits, Prof. Sermon.
KURT JACOBS. “Genomic integrity of human embryonic stem cells: low-grade mosaicism and the effect of culture density”. 8/01/2015. Supervisors: Prof. Spits, Prof. Sermon.
HA NGUYEN THI. “Genetic instability in human embryonic stem cells: microsatellite instability and key driver genes of recurrent chromosomal abnormalities”. 6/01/2015. Supervisor: Prof. Spits.