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| Status |
Public on Nov 15, 2014 |
| Title |
Transcriptional and epigenetic program changes of induced beta cells over time [RRBS-seq] |
| Organism |
Mus musculus |
| Experiment type |
Methylation profiling by high throughput sequencing
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| Summary |
Direct lineage conversion is a promising approach to generate therapeutically important cell types for disease modeling and tissue repair. However, it is often unclear whether lineage-reprogrammed cells remain stable long-term and whether the properties of the reprogrammed cells evolve over time. Here, using an improved method of converting pancreatic acinar cells to beta-cells, we show that induced beta-cells persist in the adult pancreas for up to 14 months and form islet-like structures. Detailed analyses of induced cells over 7 months reveal that global DNA methylation changes occur rapidly whereas transcription network remodeling evolves over two months to resemble that of endogenous beta-cells and then stabilizes thereafter. Progressive gain of beta-cell function by converted cells during the 7 month period coincides with both transcriptional changes and the formation of islet-like structures. These studies demonstrate the ability of lineage-reprogrammed cells to achieve a stable state and identify key cellular and molecular milestones during their long-term evolution.
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| Overall design |
Acinar cells and beta cells were collected as control, as well as induced beta cell samples at day 10, day 30, day 60, and 7 months
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| Contributor(s) |
Li W, Zhu J, Zhang Y, Clement K, Zhou Q |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Jul 21, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Kendell Clement |
| Organization name |
Harvard University
|
| Lab |
Meissner Lab
|
| Street address |
7 Divinity Ave.
|
| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02138 |
| Country |
USA |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA255762 |
| SRA |
SRP044672 |
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