title: Multipotent adult germline stem cells and embryonic stem cells functional proteomics revealed an important role of eukaryotic initiation factor 5A (Eif5a) in stem cell differentiation.
abstract: Multipotent adult germline stem cells (maGSCs) are pluripotent cells that can be differentiated into somatic cells of the three primary germ layers. To highlight the protein profile changes associated with stem cell differentiation, retinoic acid (RA) treated mouse stem cells (maGSCs and ESCs) were compared to nontreated stem cells. 2-DE and DIGE reference maps were created, and differentially expressed proteins were further processed for identification. In both stem cell types, the RA induced differentiation resulted in an alteration of 36 proteins of which 18 were down-regulated and might be potential pluripotency associated proteins, whereas the other 18 proteins were up-regulated. These might be correlated to stem cell differentiation. Surprisingly, eukaryotic initiation factor 5A (Eif5a), a protein which is essential for cell proliferation and differentiation, was significantly down-regulated under RA treatment. A time-dependent investigation of Eif5a showed that the RA treatment of stem cells resulted in a significant up-regulation of the Eif5a in the first 48 h followed by a progressive down-regulation thereafter. This effect could be blocked by the hypusination inhibitor ciclopirox olamine (CPX). The alteration of Eif5a hypusination, as confirmed by mass spectrometry, exerts an antiproliferative effect on ESCs and maGSCs in vitro, but does not affect the cell pluripotency. Our data highlights the important role of Eif5a and its hypusination for stem cell differentiation and proliferation.
authors.affiliation: Department of Nephrology and Rheumatology, Georg-August University Goettingen , Robert-Koch-Strasse 40, D-37075 Goettingen, Germany. dihazi@med.uni-goettingen.de
authors.forename: Hassan
authors.initials: H
authors.lastname: Dihazi
authors.forename: Gry H
authors.initials: GH
authors.lastname: Dihazi
authors.forename: Olaf
authors.initials: O
authors.lastname: Jahn
authors.forename: Sandra
authors.initials: S
authors.lastname: Meyer
authors.forename: Jessica
authors.initials: J
authors.lastname: Nolte
authors.forename: Abdul R
authors.initials: AR
authors.lastname: Asif
authors.forename: Gerhard A
authors.initials: GA
authors.lastname: Mueller
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Engel
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D000077768:Ciclopirox; D005854:Germ Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D053605:Leukemia Inhibitory Factor / Q000494:pharmacology; D008297:Male; D051379:Mice; D010448:Peptide Initiation Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D020543:Proteome / Q000032:analysis; D040901:Proteomics / Q000379:methods*; D011728:Pyridones / Q000494:pharmacology; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology; D057825:Two-Dimensional Difference Gel Electrophoresis / Q000379:methods; D000097574:Eukaryotic Translation Initiation Factor 5A
chemical_list: D000935:Antifungal Agents; D000970:Antineoplastic Agents; D000077768:Ciclopirox; D053605:Leukemia Inhibitory Factor; D010448:Peptide Initiation Factors; D020543:Proteome; D011728:Pyridones; D016601:RNA-Binding Proteins; D014212:Tretinoin; D000097574:Eukaryotic Translation Initiation Factor 5A