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Generation of β Cells from iPSC of a MODY8 Patient with a Novel Mutation in the Carboxyl Ester Lipase (CEL) Gene
- Source :
- J Clin Endocrinol Metab.
- Publication Year :
- 2021
- Publisher :
- The Endocrine Society, 2021.
-
Abstract
- ContextMaturity-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.MethodsA genetic study was performed in a patient suspected of monogenic diabetes.ResultsA 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.ConclusioniPSC 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.
- Subjects :
- Adult
Male
Heterozygote
medicine.medical_specialty
Endocrinology, Diabetes and Metabolism
DNA Mutational Analysis
Induced Pluripotent Stem Cells
Primary Cell Culture
Clinical Biochemistry
Cell
Context (language use)
Enteroendocrine cell
induced pluripotent stem cells (iPSC)
medicine.disease_cause
Biochemistry
Endocrinology
stem cells
Insulin-Secreting Cells
Internal medicine
medicine
Humans
Induced pluripotent stem cell
Gene
Cells, Cultured
Mutation
diabetes
Chemistry
Biochemistry (medical)
Cell Differentiation
Lipase
Molecular biology
MODY (monogenic diabetes of the young)
In vitro
beta cells
medicine.anatomical_structure
Diabetes Mellitus, Type 2
Genetic Techniques
Stem cell
Subjects
Details
- ISSN :
- 19457197 and 0021972X
- Volume :
- 106
- Database :
- OpenAIRE
- Journal :
- The Journal of Clinical Endocrinology & Metabolism
- Accession number :
- edsair.doi.dedup.....3305f5b5b10f20ce401b8740767c2d21