PXD015955 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | in vivo environment swiftly restricts human pancreatic progenitors towards monohormonal identity via a HNF1A/HNF4A mechanism |
Description | Generating insulin-producing β-cells from human induced pluripotent stem cells is a promising cell replacement therapy aimed at improving or curing certain forms of diabetes. Nevertheless, despite important recent advances, the efficient production of functionally mature β-cells is yet to be achieved, with most current differentiation protocols generating a heterogeneous population comprising of subpopulation of cells expressing different islet hormones, including hybrid polyhormonal entities. A solution to this issue is transplanting end-stages differentiating cells into living hosts, which was demonstrated to majorly improve β-cell maturation. Yet, to date, the cellular and molecular mechanisms underlying the transplanted cells response to the in vivo environment exposure was not yet properly characterized. Here we use global proteomics and large-scale imaging techniques aimed at demultiplexing and filtering cellular processes and molecular signatures modulated by the immediate in vivo effect. We show that in vivo exposure swiftly confines in vitro generated human pancreatic progenitors to single hormone expression. The global proteome landscape of the transplanted cells was closer to the one presented by native human islets, especially in regard to energy metabolism and redox balance. Moreover our study indicates a possible link between these processed and certain epigenetic regulators involved in maintenance and propagation of the islet cells identity. Pathway analysis predicted HNF1A and HNF4A as key regulators controlling the in vivo islet-promoting response, with experimental evidence confirming their involvement in confining islet cell identity. To our knowledge this is the first study demultiplexing the immediate response of the transplanted pancreatic progenitors to in vivo exposure. |
HostingRepository | PRIDE |
AnnounceDate | 2020-02-12 |
AnnouncementXML | Submission_2020-02-12_05:44:25.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 | TMT6plex-126 reporter+balance reagent acylated residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2019-10-22 01:40:27 | ID requested | |
⏵ 1 | 2020-02-12 05:44:26 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: Human, iPSC, alginate, in vivo transplant |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD015955
- Label: PRIDE project
- Name: in vivo environment swiftly restricts human pancreatic progenitors towards monohormonal identity via a HNF1A/HNF4A mechanism