PXD015955

PXD015955 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2019-10-22 01:40:27	ID requested
⏵ 1	2020-02-12 05:44:26	announced

Dataset with its publication pending

submitter keyword: Human, iPSC, alginate, in vivo transplant

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. PXD015955
     1. Label: PRIDE project
     2. Name: in vivo environment swiftly restricts human pancreatic progenitors towards monohormonal identity via a HNF1A/HNF4A mechanism