Exploring The Pathogenetic Basis of ICF Syndrome With Human Induced Pluripotent Stem Cells

Stem cells have arisen as a model system to uncover molecular and pathogenic mechanisms underlying many human diseases such as immunodeficiency, neurodegenerative disorders and cancer. Many of these disorders are due the dysfunction of DNA methylation, a DNA modification mechanism involved in regulating gene activity. Emerging technology demonstrated that patient skin cells can be converted into induced pluripotent stem cells, thus generating patient specific stem cells. We propose to exploit human stem cells containing genetic mutations in DNA methylation machinery, like those deriving from Immunodeficiency, Centromeric instability, Facial anomalies (ICF) syndrome affected patients. This allows to study the molecular disturbances of the immune system response that are associated to the defects in DNA methylation. As DNA methylation alterations are linked with several human diseases, we anticipate learning more broaden biology from this human stem cell study. Finally, this study will shed light on the potentialities of a cell-based therapy in curing these types of human diseases. Our proposal research will be an important step to translate stem cell research into future clinical applications, such as the use of induced pluripotent stem cells for curing immnuodeficiency, that is the most severe clinical sign of ICF affected individuals and representing the main cause of their death at young age.