Silvia Pellegrini, Giovanni B Pipitone, Alessandro Cospito, Fabio Manenti, Gaia Poggi, Marta T Lombardo, Rita Nano, Gianvito Martino, Maurizio Ferrari, Paola Carrera, Valeria Sordi, Lorenzo Piemonti
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages e2322–e2333
https://doi.org/10.1210/clinem/dgaa986
Maturity-onset diabetes of the young (MODY) 8 is a rare form of monogenic diabetes characterized by a mutation in CEL (carboxyl ester lipase) gene, which leads to exocrine pancreas dysfunction, followed by β-cell failure. Induced pluripotent stem cells can differentiate into functional β cells. Thus, β cells from MODY8 patients can be generated in vitro and used for disease modelling and cell replacement therapy.
A genetic study was performed in a patient suspected of monogenic diabetes.
A novel heterozygous pathogenic variant in CEL (c.1818delC) was identified in the proband, allowing diagnosis of MODY8. Three MODY8-iPSC (induced pluripotent stem cell) clones were reprogrammed from skin fibroblasts of the patient, and their pluripotency and genomic stability confirmed. All 3 MODY8-iPSC differentiated into β cells following developmental stages. MODY8-iPSC–derived β cells were able to secrete insulin upon glucose dynamic perifusion. The CEL gene was not expressed in iPSCs nor during any steps of endocrine differentiation.
iPSC lines from a MODY8 patient with a novel pathogenic variant in the CEL gene were generated; they are capable of differentiation into endocrine cells, and β-cell function is preserved in mutated cells. These results set the basis for in vitro modelling of the disease and potentially for autologous β-cell replacement.
We provide our journal authors with a variety of resources for increasing the discoverability and citation of their published work. Use these tools and tips to broaden the impact of your article.
Read our special collections of Endocrine Society journal articles, curated by topic, Altmetric Attention Scores, and Featured Article designations.