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| Status |
Public on Jun 01, 2019 |
| Title |
Loss-of-function due to MODY1/HNF4A mutation abrogates liver and pancreas differentiation from MODY1-hiPSCs |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Purpose: To investigate the impact of MODY1/HNF4A mutation on foregut development using differentiated control and MODY1-hiPSCs
Methods: RNA-Seq was performed on foregut/hepato-pancreatic progenitors obtained on day 14 of the directed differentiation of hiPSCs from MODY1 patients (3 clones from iN904-1, 1 clone from iN904-2) and family controls (3 clones from iN904-7, 2 clones from iN904-13). Differential expression analysis, KEGG pathway and gene ontology analyses were carried out. qRT-PCR validation was also performed using SYBR Green assays.
Results: RNA-Seq and transcriptional analyses revealed that numerous foregut liver- and pancreas-related genes, including HNF4A, were downregulated in MODY1-hiPSC-derived hepato-pancreatic progenitors with a fold change ≥1.5 and p value <0.05, whereas hindgut HOX genes were upregulated. Altered expression of a number of genes were further confirmed with qRT-PCR.
Conclusions: The HNF4A loss-of-function mutation (p.Ile271fs) resulted in significantly reduced HNF4A expression or HNF4A haploinsufficiency, affecting the proper development of the foregut and its derivatives. This deficiency is propagated to both hepatic and pancreatic cell fates, and may account for β cell developmental defects and the progressive deterioration of β cell function in MODY1.
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| Overall design |
RNA-Seq was performed on foregut/hepato-pancreatic progenitors obtained on day 14 of the directed differentiation of hiPSCs from MODY1 patients (3 clones from iN904-1, 1 clone from iN904-2) and family controls (3 clones from iN904-7, 2 clones from iN904-13).
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| Contributor(s) |
Ng HJ, Jasmen J, Lim CS, Lau HH, Krishnan VG, Kulkarni RN, Raeder H, Vallier L, Hoon S, Teo KK |
| Citation(s) |
31195238 |
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| Submission date |
Oct 30, 2017 |
| Last update date |
Jun 17, 2019 |
| 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) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA416326 |
| SRA |
SRP122933 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE106335_All-output.xlsx |
1.9 Mb |
(ftp)(http) |
XLSX |
| GSE106335_All_Counts.forR.xlsx |
3.1 Mb |
(ftp)(http) |
XLSX |
| GSE106335_All_FPKM.forR.txt.gz |
815.8 Kb |
(ftp)(http) |
TXT |
| GSE106335_All_FPKM_protein_coding_GRCh38.tsv.gz |
1.0 Mb |
(ftp)(http) |
TSV |
| GSE106335_targets.txt.gz |
140 b |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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