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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jan 30, 2024 |
| Title |
ISR inhibition reverses pancreatic β-cell failure in Wolfram syndrome models |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Pancreatic β-cell failure induced by WFS1 deficiency is manifested in wolfram syndrome (WS). The lack of a suitable human model in WS has hampered the progress in developing new treatments. Here, human pluripotent stem cell derived pancreatic β cells (SC-β cells) harboring WFS1-deficiency and mouse model of β cell-specific Wfs1 knockout were applied to model β-cell failure in WS. Single-cell RNA sequencing of WFS1-deficient SC-β cells revealed two cell fates along pseudotime trajectory including maturation and stress branch. WFS1 deficiency blocked β-cell fate trajectory to maturation but pushed it towards stress trajectory leading to β-cell failure.
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| Overall design |
We generated hESCs reporter cell line (MEL1 Nkx6.1:linker2a:mCherry; INSGFP/w) that enable to precisely and dynamically trace SC-β cells during differentiated stages. Meanwhile, WFS1 knockout hESCs reporter cell line (WFS1-/-) was established by using a CRISPR/Cas9 knock-out strategy to mimic severe mutations identified from WS patients. We performed single-cell RNA sequencing (scRNA-Seq) for WT and WFS1-/- SC-islets by sorting out GFP and mCherry double-positive SC-β cells with high INS and NKX6.1 expression
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| Contributor(s) |
Hu R, Chen X, Su Q, Wang Z, Wang X, Xu M, Zhang Z, Shao L, Li W |
| Citation(s) |
38321214 |
| Submission date |
Jun 20, 2023 |
| Last update date |
Mar 20, 2024 |
| Contact name |
Xiangyi Chen |
| Organization name |
Weida Li
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| Street address |
No. 1239, Siping Road, Shanghai, China
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| City |
Shanghai |
| ZIP/Postal code |
200092 |
| Country |
China |
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| Platforms (1) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA985707 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE235331_RAW.tar |
70.6 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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