Establishing iPSCs as a method to model neurodevelopment in Down’s syndrome

The derivation of pluripotent stem cells (now termed induced pluripotent stem cells, iPSC) from mature somatic cells was a finding of seminal importance to fundamental cell biology. Being pluripotent (able to differentiate into every cell type present in the adult animal body) and sharing most other characteristics with embryonic stem cells, but being much readier obtainable and their derivation free from ethical restraints, human induced pluripotent stem cells (hiPSC) provide access to cell types and insights into cell processes previously unattainable to researches. For this thesis, a hiPSC line was established from a skin biopsy donated by a Down’s syndrome patient. Having access to human pluripotent cells able to recapitulate the events of early neurogenesis in individuals with this disorder is invaluable to the understanding of its mechanisms. In parallel, work has been performed on optimizing iPSC reprogramming protocol. By exchanging one of the transcription factors used for reprogramming with a reporter gene, genomic integration of reprogramming factors has become possible to be traced visually, enabling more efficient selection of reprogrammed iPSC colonies.