|
| Status |
Public on Jan 21, 2022 |
| Title |
Single-cell RNA sequencing reveals a role for reactive oxygen species and peroxiredoxins in fatty-acid-induced rat ß-cell proliferation |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
The functional mass of insulin-secreting pancreatic β cells expands to maintain glucose homeostasis in the face of nutrient excess, in part via replication of existing β cells. To decipher the underlying molecular mechanisms, we assessed β-cell proliferation in isolated rat islets exposed to glucose and oleate or palmitate for 48 h and analyzed the transcriptional response by single-cell RNA sequencing. Unsupervised clustering of pooled β cells identified subpopulations, including proliferating β cells. β-cell proliferation increased in response to oleate but not palmitate. Both fatty acids enhanced the expression of genes involved energy metabolism and mitochondrial activity. Comparison of proliferating vs. non-proliferating β cells and pseudotime ordering suggested the involvement of reactive oxygen species (ROS) and peroxiredoxin signaling. Accordingly, the antioxidant N-acetyl cysteine and the peroxiredoxin inhibitor Conoidin A both blocked oleate-induced β-cell proliferation. Our data reveal a key role for ROS signaling in β-cell proliferation in response to nutrients.
|
| |
|
| Overall design |
Isolated rat pancreatic islets were treated for 48h in the presence of 16,7mM glucose (VEH; 4 replicates), 16,7mM glucose + 0.5mM palmitate (PAL; 3 biological replicates) or oleate (OL; 4 biological replicates) prior single cell RNA-sequencing
|
| |
|
| Contributor(s) |
Vivoli A, Ghislain J, Filali-Mouhim A, Sladek R, Poitout V |
| Citation(s) |
36191509 |
| |
| Submission date |
Jan 18, 2022 |
| Last update date |
Oct 11, 2022 |
| Contact name |
Alexis Vivoli |
| E-mail(s) |
alexis.vivoli@umontreal.ca
|
| Organization name |
Centre de recherche du centre hospitalié de l'université de montréal (CRCHUM)
|
| Street address |
900 rue St denis
|
| City |
Montréal |
| State/province |
Québec |
| ZIP/Postal code |
H2X0A9 |
| Country |
Canada |
| |
|
| Platforms (1) |
| GPL25947 |
Illumina NovaSeq 6000 (Rattus norvegicus) |
|
| Samples (11)
|
|
| Relations |
| BioProject |
PRJNA798232 |
Less...
More...