 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Jan 24, 2020 |
| Title |
In vivo hyperglycemia exposure elicits distinct period-dependent effects on human pancreatic progenitor differentiation, conveyed by oxidative stress |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Aim: The loss of insulin-secreting β-cells, ultimately characterizing most diabetes forms, demands the development of cell replacement therapies. The common endpoint for all ex vivo strategies is transplantation into diabetic patients. However, the effects of hyperglycemia environment on the transplanted cells were not yet properly assessed. Thus, the main goal of this study was to characterize global effect of brief and prolonged in vivo hyperglycemia exposure on the cell fate acquisition and maintenance of transplanted human pancreatic progenitors.
Methods: To rigorously study the effect of hyperglycemia, in vitro differentiated human induced pluripotent stem cells (hiPSC)-derived pancreatic progenitors were xenotransplanted in normoglycemic and diabetic NSG RIP-DTR mice. The transplants were retrieved after one-week or one-month exposure to overt hyperglycemia and analyzed by large-scale microscopy or global proteomics. For this study we pioneer the use of the NSG RIP-DTR system in the transplantation of hiPSC, making use of its highly reproducible specific and absolute β-cell ablation property in the absence of inflammation or other organ toxicity.
Results: Here we show for the first time that besides the presence of an induced oxidative stress signature, the cell fate and proteome landscape response to hyperglycemia was different, involving largely different mechanisms, according to the period spent in the hyperglycemic environment. Surprisingly, brief hyperglycemia exposure increased the bihormonal cell number by impeding the activity of specific islet lineage determinants. Moreover it activated antioxidant and inflammation protection mechanisms signatures in the transplanted cells. In contrast, the prolonged exposure was characterized by decreased numbers of hormone+ cells, low/absent detoxification signature, augmented production of oxygen reactive species and increased apoptosis.
Conclusion: Hyperglycemia exposure induced distinct, period-dependent, negative effects on xenotransplanted human pancreatic progenitor, affecting their energy homeostasis, cell fate acquisition and survival.
|
| |
|
| Overall design |
hiPSCs were differantiated towards S5 pancreatic progenitor cells and S7 beta-like cells following the protocol by Rezania 2014
|
| |
|
| Contributor(s) |
Legøy TA, Ghila L, Vethe H, Abadpour S, Mathiesen AF, Paulo JA, Scholz H, Ræder H, Chera S |
| Citation(s) |
31942009 |
| |
| Submission date |
Dec 02, 2019 |
| Last update date |
Jan 24, 2020 |
| Contact name |
Simona Chera |
| E-mail(s) |
Simona.Chera@uib.no
|
| Organization name |
University of Bergen
|
| Street address |
Haukelandsbakken 15
|
| City |
Bergen |
| ZIP/Postal code |
5021 |
| Country |
Norway |
| |
|
| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
|
| Samples (14)
|
|
| Relations |
| BioProject |
PRJNA593037 |
| SRA |
SRP234446 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE141309_Normalized_Expression_All_Samples.csv.gz |
2.5 Mb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
|
|
|
|
 |
Less...
More...