Reprogramming somatic cells into iPS cells to generate an in vitro model system of Amyotrophic Lateral Sclerosis (ALS)

Gruppo di Ricerca: 
A. Rosa, J. Lenzi, M. Morlando, O. Sthandier, I. Bozzoni
Attach English: 

Amyotrophic Lateral Sclerosis (ALS) is one of the most severe neurodegenerative disorders, due to the loss of upper and lower motor neurons. A subset of familial ALS cases is linked to mutations in the FUS/TLS and TARDP genes, both encoding for putative regulators of microRNA (miRNA) biogenesis. In the nervous system, miRNAs fine-tune neuronal gene expression in a spatially and temporally restricted manner and deregulation of specific miRNAs correlates with the initiation and progression of several neurological disorders. Our general aim is to study the possible involvement of miRNAs in ALS pathogenesis.

It was recently reported that human somatic adult cells, such as skin fibroblasts, can be reprogrammed to an embryonic stage, known as induced pluripotent stem cells (iPSCs). Such iPSCs closely resemble human Embryonic Stem Cells (hESCs), since they can be indefinitely propagated in vitro and differentiated in all adult tissues.As iPSCs can be also generated from somatic cells derived from patients harboring genetic diseases (patient-specific iPSCs), they provide a unique opportunity for human disease modeling in vitro.

One of the major problems with the molecular analysis of the ALS-associated mutations is the lack of suitable cellular model systems. In order to circumvent this issue, our approach consists in the generation of iPSC lines from fibroblasts of ALS patients, which can be differentiated into genetically matched motor neurons. A collection of ALS-iPS covering several FUS/TLS and TARDP mutations is now available in our lab and can be exploited for the analysis of possible alteration of RNA metabolism in ALS motor neurons.

Anno del Convegno: 
2012

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