Lack of ABCG2 expression and side population properties in human pluripotent stem cells.
The multidrug transporter ABCG2 in cell membranes enables various stem cells and cancer cells to efflux chemicals, including the fluorescent dye Hoechst 33342. The Hoechst(-) cells can be sorted out as a side population with stem cell properties. Abcg2 expression in mouse embryonic stem cells (ESCs) reduces accumulation of DNA-damaging metabolites in the cells, which helps prevent cell differentiation. Surprisingly, we found that human ESCs do not express ABCG2 and cannot efflux Hoechst. In contrast, trophoblasts and neural epithelial cells derived from human ESCs are ABCG2(+) and Hoechst(-). Human ESCs ectopically expressing ABCG2 become Hoechst(-), more tolerant of toxicity of mitoxantrone, a substrate of ABCG2, and more capable of self-renewal in basic fibroblast growth factor (bFGF)-free condition than control cells. However, Hoechst(low) cells sorted as a small subpopulation from human ESCs express lower levels of pluripotency markers than the Hoechst(high) cells. Similar results were observed with human induced pluripotent stem cells. Conversely, mouse ESCs are Abcg2(+) and mouse trophoblasts, Abcg2(-). Thus, absence of ABCG2 is a novel feature of human pluripotent stem cells, which distinguishes them from many other stem cells including mouse ESCs, and may be a reason why they are sensitive to suboptimal culture conditions.
Zeng
Hui
H
Department of Genetics and Developmental Biology, University of Connecticut Stem Cell Institute, University of Connecticut Health Center, Farmington, Connecticut 06030, USA.
Park
Jung Woo
JW
Guo
Min
M
Lin
Ge
G
Crandall
Leann
L
Compton
Tiwanna
T
Wang
Xiaofang
X
Li
Xue-Jun
XJ
Chen
Fang-Ping
FP
Xu
Ren-He
RH
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000633:toxicity; D001562:Benzimidazoles / Q000378:metabolism* / Q000494:pharmacology; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003470:Culture Media / Q000494:pharmacology; D004249:DNA Damage / Q000187:drug effects / Q000502:physiology*; D004351:Drug Resistance / Q000502:physiology*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008942:Mitoxantrone / Q000378:metabolism / Q000633:toxicity; D009363:Neoplasm Proteins / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D013045:Species Specificity; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D001562:Benzimidazoles; D003470:Culture Media; D009363:Neoplasm Proteins; D016222:Fibroblast Growth Factor 2; D008942:Mitoxantrone; C017807:bisbenzimide ethoxide trihydrochloride