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| Status |
Public on Feb 16, 2017 |
| Title |
Converting adult pancreatic α-cells into β-cells by targeting Dnmt1 and Arx |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
After their destruction in adult mice, insulin-producing pancreatic beta-cells slowly regenerate from other islet cells, like glucagon-producing alpha-cells. However the molecular basis of this conversion is unknown. Moreover it remains unclear if this intra-islet cell conversion is relevant to human diseases with extensive beta-cell loss, like in type 1 diabetes (T1D). Here, we show that subsets of glucagon-expressing cells in subjects with T1D produce Insulin and other molecular features of beta-cells, accompanied by loss of the alpha-cell regulators DNA methyltransferase 1 (Dnmt1) and Aristaless-related homeobox (Arx). We generated mice permitting lineage tracing and inactivation of Dnmt1 and Arx in adult alpha-cells. Within 3 months of Dnmt1 and Arx loss, 50% of alpha-cells converted into cells producing insulin protein but not glucagon, changes not observed in alpha-cells after only Arx or Dnmt1 loss. Single cell isolation and high-throughput RNA sequencing revealed efficient and extensive alpha-cell conversion into progeny indistinguishable by global gene expression from native beta-cells. Our work reveals pathways regulated by Arx and Dnmt1 sufficient for achieving targeted generation of beta-cells from adult pancreatic alpha-cells.
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| |
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| Overall design |
Single-cell RNA-seq of in-vivo conversion of pancreatic α-cells into β-cells
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| |
|
| Contributor(s) |
Enge M, Chakravarthy H |
| Citation(s) |
28215845 |
| Submission date |
Mar 21, 2016 |
| Last update date |
Sep 05, 2019 |
| Contact name |
Martin Enge |
| E-mail(s) |
martin.enge@gmail.com
|
| Organization name |
Stanford University
|
| Department |
Bioengineering
|
| Lab |
Stephen Quake
|
| Street address |
James H. Clark Center, 318 Campus Drive,
|
| City |
Stanford |
| State/province |
CA |
| ZIP/Postal code |
94305 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (182)
|
|
| Relations |
| BioProject |
PRJNA316075 |
| SRA |
SRP072214 |
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