The ability to differentiate human embryonal stem cells (hESC) and induced pluripotent stem cells (hiPSC) into virtually any cell type has enabled the creation of cellular models of diseases for which human cells are not readily accessible. Using these strategies, we have examined the molecular pathogenesis of monogenic forms of diabetes such as Wolframs syndrome and various MODYs using stem cell-derived insulin producing cells created from fibroblasts of patients with these disorders. Our recent development of a protocol for the generation of arcuate-type hypothalamic neurons from somatic cells of human subjects has enabled us to study the neurobiology of disorders such as Bardet-Biedl and Prader Willi syndromes, as well as disorders of proconvertase 1 activity. Using Crispr/Cas, we have both corrected beta cell and neuronal mutations in affected cell lines, and introduced mutations into unaffected cell lines. Such experiments allow the analysis of gene-gene interactions, the screening of molecules that may mitigate specific cellular phenotypes, and could ultimately provide transplantable cells for treatment of disease.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology