Dataset Information

In vivo hyperglycemia exposure elicits distinct period-dependent effects on human pancreatic progenitor differentiation, conveyed by oxidative stress

ABSTRACT: Objective: 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.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Stem Cell, Cell Culture

DISEASE(S): Disease Free

SUBMITTER: Thomas Aga Legøy

LAB HEAD: Simona Chera

PROVIDER: PXD015071 | Pride | 2020-02-12

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	384462_a13009_HeidTAL.mzIdentML	Mzid
	384470_a13000_HeidTAL.mzIdentML	Mzid
	384471_a12999_HeidTAL.mzIdentML	Mzid
	384472_a12998_HeidTAL.mzIdentML	Mzid
	384474_a12997_HeidTAL.mzIdentML	Mzid

Items per page:

1 - 5 of 56

Publications

In vivo hyperglycaemia exposure elicits distinct period-dependent effects on human pancreatic progenitor differentiation, conveyed by oxidative stress.

Legøy Thomas A TA Ghila Luiza L Vethe Heidrun H Abadpour Shadab S Mathisen Andreas F AF Paulo Joao A JA Scholz Hanne H Raeder Helge H Chera Simona S

Acta physiologica (Oxford, England) 20200108 4

<h4>Aim</h4>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 hyperglycaemia 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 hyperglycaemia exposure on the cell fate acquisit ...[more]

PMID: 31872528

Similar Datasets

Project description: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.