Genomic instability of human pluripotent stem cells
Human pluripotent stem cells (hPSC) are either derived from discarded human embryos at the blastocyst stage (human embryonic stem cells (hESC)), or obtained by reprograming human fibroblasts into human induced pluripotent stem cells (hiPS). As hPSC can differentiate into virtually any cell type of the body, they are an ideal source of mature cells to study normal and pathological human development in vitro. They are also a promising source of cells for regenerative medicine.
1. Genomic instability in hPSC
Recent evidence suggests that PSC might present genetic abnormalities that arise during cell culture or cell reprogramming. These abnormalities are a serious concern for their in vitro use or clinical applications. While human embryonic stem cells are karyotypically normal at derivation, aneuploid hESC clones can appear during cell culture. Copy number variations have also been detected by using microarrays. It is speculated that these abnormalities bestow a growth advantage and that, as a consequence, these cells are selected during cell culture. Several factors could influence the incidence of these genetic aberrations, such as the duration and the type of culture conditions. It is not known the speed at which these abnormalities arise, the determinism of such events, nor the underlying mechanisms.
Objectives: Mapp mutagenic events that occur during cell culture in iPSC using microarrays, RNA-seq data and whole genome sequencing; identify the timing of incidence of mutagenic event and the impact of cell culture conditions; link adaptation to culture-induced cellular stress and mutagenic events.
2. Differentiation of human pluripotent stem cell into bronchial epithelial cells : lung in a dish
hPSC are a unique tool to model human normal development and disease. In close collaboration with the Department of Lung diseases of the University Hospital of Montpellier, we develop a protocol to differentiate hPSC into bronchial epithelial cells.
Objectives : obtain a proof of concept of in vitro lung disease modelling by differentiating iPS from a patient with primary ciliary dyskinesia into ciliated bronchial epithelium cells.
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More references, click on PubMed:
John DE VOS
DE VOS John (PUPH/UM)
RAMIREZ Jean-Marie (MCF/UM)
ASSOU Said (IR/UM)
AHMED Engi (Doctorante/1ère année)
BOUCKENHEIMER Julien (Doctorant/2ème année)
SANSAC Caroline (Doctorante/2ème année)
pluripotent stem cells
embryonic stem cells
induced pluripotent stem cells
pluripotent stem cell culture
bronchial epithelium differentiation