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Status |
Public on Feb 24, 2022 |
Title |
Robust Expansion of Human Pancreatic Progenitors by Small Molecules [RNA-seq] |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
An unlimited source of functional human pancreatic β cells are in highly demand. Even with recent advances in pancreatic β-like cell differentiation from human pluripotent stem cells (hPSCs), several hurdles obviously remain and the differentiation protocols need to be further improved. Chemical strategies are particularly useful to address these challenges. Here, through chemical screening, we unexpectedly identified that BET bromodomain inhibitor I-BET151 could robustly promote the expansion of PDX1 and NKX6.1 double-positive human pancreatic progenitors (PPs). These hPSC-derived expandable pancreatic progenitors (ePPs) can proliferate extensively in a chemically defined condition with I-BET151. Even after long-term expansion, these ePPs maintain pancreatic progenitor cell status. In addition, ePPs can efficiently differentiate into pancreatic β-like cells (ePP-β cells). These ePP-β cells are functional and demonstrate glucose-stimulation insulin-secretion (GSIS) capacity. Mechanistically, I-BET151 can activate Notch signaling and promote the expression of key pancreatic progenitor-associated genes and transcriptional network. Conclusively, our studies achieve the long-term goal of robust expansion of human pancreatic progenitors and represent a significant step towards unlimited supplies of functional human pancreatic β cells that are of great interest for biomedical research and regenerative medicine.
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Overall design |
RNA-seq of cells at defined developmental stages from stem cells to pancreatic β-like cells.RNA-seq of ePP-P9, ePP-P21 and ePP-derived pancreatic β-like cells. RNA-seq of PPs treated with DMSO or I-BET151.
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Contributor(s) |
Ma X, Lu Y, Zhou Z, Zhu S |
Citation(s) |
35196077 |
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Submission date |
Aug 23, 2020 |
Last update date |
Feb 25, 2022 |
Contact name |
Yunkun Lu |
Organization name |
Zhejiang University
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Department |
Life Sciences Institute
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Street address |
866 Yuhangtang Rd.
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City |
Hangzhou |
State/province |
Zhejiang |
ZIP/Postal code |
310058 |
Country |
China |
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Platforms (1) |
GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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Samples (14)
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This SubSeries is part of SuperSeries: |
GSE156712 |
Robust Expansion of Human Pancreatic Progenitors by Small Molecules |
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Relations |
BioProject |
PRJNA658807 |
SRA |
SRP278531 |