title: Dynamic ABCG2 expression in human embryonic stem cells provides the basis for stress response.
abstract: ABCG2 is a plasma membrane multidrug transporter with an established role in the cancer drug-resistance phenotype. This protein is expressed in a variety of tissues, including several types of stem cell. Although ABCG2 is not essential for life, knock-out mice were found to be hypersensitive to xenobiotics and had reduced levels of the side population of hematopoietic stem cells. Previously we have shown that ABCG2 is present in human embryonic stem cell (hESC) lines, with a heterogeneous expression pattern. In this study we examined this heterogeneity, and investigated whether it is related to stress responses in hESCs. We did not find any difference between expression of pluripotency markers in ABCG2-positive and negative hESCs; however, ABCG2-expressing cells had a higher growth rate after cell separation. We found that some harmful conditions (physical stress, drugs, and UV light exposure) are tolerated much better in the presence of ABCG2 protein. This property can be explained by the transporter function which eliminates potential toxic metabolites accumulated during stress conditions. In contrast, mild oxidative stress in hESCs caused rapid internalization of ABCG2, indicating that some environmental factors may induce removal of this transporter from the plasma membrane. On the basis of these results we suggest that a dynamic balance of ABCG2 expression at the population level has the advantage of enabling prompt response to changes in the cellular environment. Such actively maintained heterogeneity might be of evolutionary benefit in protecting special cell types, including pluripotent stem cells.
authors.affiliation: Membrane Research Group of the Hungarian Academy of Sciences, Semmelweis, University and National Blood Center, Diószegi u. 64., 1113, Budapest, Hungary.
authors.forename: Zsuzsa
authors.initials: Z
authors.lastname: Erdei
authors.forename: Balázs
authors.initials: B
authors.lastname: Sarkadi
authors.forename: Anna
authors.initials: A
authors.lastname: Brózik
authors.forename: Kornélia
authors.initials: K
authors.lastname: Szebényi
authors.forename: György
authors.initials: G
authors.lastname: Várady
authors.forename: Veronika
authors.initials: V
authors.lastname: Makó
authors.forename: Adrienn
authors.initials: A
authors.lastname: Péntek
authors.forename: Tamás I
authors.initials: TI
authors.lastname: Orbán
authors.forename: Ágota
authors.initials: Á
authors.lastname: Apáti
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism*; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D005786:Gene Expression Regulation / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000528:radiation effects; D021381:Protein Transport / Q000187:drug effects / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects; D015262:Xenobiotics / Q000494:pharmacology
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D009363:Neoplasm Proteins; D015262:Xenobiotics