PXD015071-2

PXD015071 is an original dataset announced via ProteomeXchange.

Title	In vivo hyperglycemia exposure elicits distinct period-dependent effects on human pancreatic progenitor differentiation, conveyed by oxidative stress
Description	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.
HostingRepository	PRIDE
AnnounceDate	2020-02-12
AnnouncementXML	Submission_2020-02-17_00:57:36.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Thomas Aga Legøy
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	dehydrated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2019-08-19 02:56:19	ID requested
1	2020-02-12 07:43:19	announced
⏵ 2	2020-02-17 00:57:38	announced	2020-02-17: Updated publication reference for PubMed record(s): 31872528.

Leg, ø, y TA, Ghila L, Vethe H, Abadpour S, Mathisen AF, Paulo JA, Scholz H, Raeder H, Chera S, In vivo hyperglycaemia exposure elicits distinct period-dependent effects on human pancreatic progenitor differentiation, conveyed by oxidative stress. Acta Physiol (Oxf), 228(4):e13433(2020) [pubmed]

submitter keyword: Human induced pluripotent stem cells, hyperglycemia, oxidative stress, LC-MS/MS

Simona Chera
contact affiliation	Department of Clinical Science, University of Bergen, Norway
contact email	Simona.Chera@uib.no
lab head
Thomas Aga Legøy
contact affiliation	University of Bergen
contact email	tle088@uib.no
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD015071
     1. Label: PRIDE project
     2. Name: In vivo hyperglycemia exposure elicits distinct period-dependent effects on human pancreatic progenitor differentiation, conveyed by oxidative stress