Age Problem Clinical Trial
Official title:
Pathology of Helicases and Premature Aging: Study by Derivation of hiPS
Topic of this work is the involvement of replicative helicases in human premature ageing syndrome. Replicative helicases are ubiquitous and essential during numerous reactions of the DNA metabolism. The family of replicative helicases (RecQL) is involved in the replication/repair of the DNA and in the telomere maintenance. There are 5 enzymes in human and 3 of them are involved in clinically recognizable syndromes: WRN for the Werner syndrome, BLM for the Bloom syndrome and RECQL4 for the Rothmund Thomson syndrome. All are responsive of a high cancer risk due to genomic instability. Molecular and cellular mechanisms involved in these diseases of ageing are unknown. Moreover, for all of them, there is not therapeutic or preventive solution.
For understanding the involved mechanisms we would like to model the 3 diseases with hiPS (human induced Pluripotent Stem cells) from somatic cells of patients. The patient recruitment was organized by the Montpellier and Nîmes public hospitals. The project is to generate a hiPS cell line for the 3 syndromes from fibroblasts and/or blood samples. Then, we could induce differentiation of hiPS to a target cell line of the diseases. Finally we could study the disease development following the genomic instability (karyotype, array-CGH) and the cellular ageing (senescence-associated heterochromatin foci, telomere length). For each mutated enzyme, we will perform a transcriptional profiling (splice, mRNA quantification) and protein studies (western blot). All results will be compared to wild type cells. ;
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