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| Status |
Public on Mar 22, 2021 |
| Title |
Decreased GLUT2 expression and defective glucose uptake in MODY3 human iPSC-Derived beta cells |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Purpose: To investigate the impact of HNF1A mutation on the development of pancreatic endocrine progenitors using differentiated control and MODY3-hiPSCs Methods: ChIP-Seq was performed on pancreatic endocrine progenitors obtained on day 20 of the directed differentiation of control hPSCs (1 clone from H9 and 3 clones from iAgB-hiPSC) and hiPSCs from MODY3 patients (3 clones from P2. Peak calling analyses were carried out. qRT-PCR validation was also performed using SYBR Green assays. Results: ChIP-Seq analysis revealed that numerous HNF1A target genes were downregulated in MODY3-hiPSC-derived pancreatic endocrine progenitors. Altered expression of a number of genes were further confirmed with qRT-PCR. Conclusions: The H126D mutation in HNF1A does not affect the expression levels of HNF1A. However, this mutation affects the DNA binding capability of the transcription factor, thereby resulting in deficiency in the gene expression of proteins that are essential to maintain normal human beta-cell function for insulin secretion.
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| Overall design |
ChIP-Seq was performed on pancreatic endocrine progenitors obtained on day 20 of the directed differentiation of hPSC of controls (1 clone from H9 and 3 clones from iAgB-hiPSCs) hiPSCs from MODY3 patients (3 clones from iP002).
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| Contributor(s) |
Low BS, Lim CS, Teo AK |
| Citation(s) |
34035238 |
| |
| Submission date |
Nov 01, 2019 |
| Last update date |
Jun 15, 2021 |
| Contact name |
Adrian Kee Keong Teo |
| E-mail(s) |
ateo@imcb.a-star.edu.sg
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| Organization name |
IMCB, A*STAR
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| Department |
Stem Cells and Diabetes Laboratory
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| Street address |
61 Biopolis Drive, Proteos
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| City |
Singapore |
| State/province |
Singapore |
| ZIP/Postal code |
138673 |
| Country |
Singapore |
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| Platforms (1) |
| GPL10999 |
Illumina Genome Analyzer IIx (Homo sapiens) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA587120 |
| SRA |
SRP227957 |
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