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| Status |
Public on Apr 05, 2013 |
| Title |
A stem cell model of diabetes due to glucokinase deficiency |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Diabetes is a disorder characterized by loss of beta cell mass and/or beta cell function, leading to deficiency of insulin relative to metabolic need. To determine whether stem cell derived-beta cells faithfully reflect the phenotypes of a diabetic subject, we generated induced pluripotent stem cells from diabetic subjects (MODY2) with heterozygous loss-of-function of the gene encoding glucokinase (GCK). These stem cells differentiated into beta cells with an efficiency comparable to controls, and expressed markers of mature beta cells, urocotin-3 and zinc transporter 8 upon transplantation into mice. While insulin secretion in response to arginine or other secretagogues was identical to cells from healthy controls, GCK mutant beta cells required higher glucose levels to stimulate insulin secretion. Importantly this glucose-specific phenotype was fully reverted upon gene sequence correction by homologous recombination. Our results demonstrate that stem cell-derived beta cells reflect beta cell-autonomous phenotypes of MODY2 subjects, providing a platform for mechanistic analysis of specific genotypes on beta cell function.
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| Overall design |
Induced pluripotent stem cells with munations in the glucokinase gene were differentiationed into pancreas cells using published protocol (D'Amour et al, 2006) with certain modifications. 1 million cells(fibroblast or stem cells or differentiated pancreatic cells) was used for RNA extraction and labeling using the Illumina total prep RNA amplification kit.
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| Contributor(s) |
Egli D, Hua H |
| Citation(s) |
23778137 |
| Submission date |
Apr 04, 2013 |
| Last update date |
Mar 20, 2017 |
| Contact name |
Haiqing Hua |
| E-mail(s) |
hua.haiqing@gmail.com
|
| Phone |
9175578165
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| Organization name |
Columbia University
|
| Street address |
3960 Broadway
|
| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10032 |
| Country |
USA |
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| Platforms (1) |
| GPL6883 |
Illumina HumanRef-8 v3.0 expression beadchip |
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| Samples (5)
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| GSM1115034 |
Induced pluripotent cells differentiated into pancreatic cells |
| GSM1115035 |
human embyonic stem cells differentiated into pancreatic cells |
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| Relations |
| BioProject |
PRJNA196306 |
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