The Cell Reprogramming Unit has two main objectives. The first, rooted in basic biology, seeks to understand how mutations in disease-causing genes influence phenotypes and key signaling pathways, using induced pluripotent stem cells (iPSCs) as a model system. The second, more translational, focuses on developing protocols for iPSC production and differentiation that can be adapted to GMP standards for clinical applications. iPSCs are chosen because they retain the patient’s genetic information, allowing the study of genotype-phenotype correlations “in vitro” that are often not faithfully replicated in murine models, where the silencing or expression of a single gene may fail to fully manifest the human phenotype.
Currently, the Unit employs two reprogramming technologies:
1) Virus-free technology: Fibroblasts obtained from skin biopsies of both healthy donors and patients are nucleofected with episomal plasmids encoding the transcription factors necessary for pluripotency.
2) Sendai virus technology: Mononuclear cells derived from blood samples are infected with the Sendai virus, which delivers the transcription factors required for inducing pluripotency.
In its early years, the Unit concentrated on establishing and refining reprogramming and differentiation protocols. Today, it is actively involved in research projects on rare neurodevelopmental disorders such as Smith-Magenis syndrome, Joubert syndrome, 4H leukodystrophy, Charcot-Marie-Tooth disease, distal focal epilepsy, Syngap1 mutation-related epilepsy, and autism. Additionally, the Unit conducts research on neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Huntington’s disease, Parkinson’s disease, and Kennedy’s disease.
