PXD013737

PXD013737 is an original dataset announced via ProteomeXchange.

Title	Total cellular proteome analysis of mutant and WT HNF4alpha Hepatic Progenitor Stage Cells
Description	Post-translational modification of proteins has been shown to control different aspects of protein biology. We have previously implicated a SUMO consensus motif in HNF4alpha’s carboxylic terminus as an important regulator of protein biology during stem cell differentiation. In this study, we have generated deletion and point mutants of HNF4alpha to precisely study the role of protein domains during hepatocyte specification. During mammalian development, liver differentiation is driven by signals which converge on multiple transcription factor networks. The hepatocyte nuclear factor signalling network is known to be essential for hepatocyte specification and maintenance. In these studies we demonstrate that nuclear HNF4 is essential for hepatic progenitor specification and the introduction of point mutations in HNF4alpha’s SUMO consensus motif leads to disrupted hepatocyte specification and maturation. Taking a multi-omics approach, we identified key deficiencies in cell biology which included; dysfunctional cell metabolism, cell adhesion, tricarboxylic acid cycle flux, mRNA transport and processing. In summary, the combination of genome editing and multi-omics analyses have provided new insight into the diverse functions of HNF4alphaprotein during human hepatocyte specification and maturation.
HostingRepository	PRIDE
AnnounceDate	2019-06-17
AnnouncementXML	Submission_2019-06-17_07:16:35.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mike Tatham
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-05-07 03:42:11	ID requested
⏵ 1	2019-06-17 07:16:36	announced

Wang Y, Tatham MH, Schmidt-Heck W, Swann C, Singh-Dolt K, Meseguer-Ripolles J, Lucendo-Villarin B, Kunath T, Rudd TR, Smith AJH, Hengstler JG, Godoy P, Hay RT, Hay DC, Protein Domain Function during Human Pluripotent Stem Cell Differentiation. iScience, 16():206-217(2019) [pubmed]

submitter keyword: Human, Embryonic Stem Cells, SUMO, Hepatic Progenitor, HNF4alpha

Ronald T Hay
contact affiliation	Professor of Molecular Biology Centre for Gene Regulation and Expression School of Life Sciences, University of Dundee, Dundee
contact email	r.t.hay@dundee.ac.uk
lab head
Mike Tatham
contact affiliation	University of Dundee
contact email	m.tatham@dundee.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD013737
     1. Label: PRIDE project
     2. Name: Total cellular proteome analysis of mutant and WT HNF4alpha Hepatic Progenitor Stage Cells