Search

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, Hoechstlow cells sorted as a small subpopulation from human ESCs express lower levels of pluripotency markers than the Hoechsthigh 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.

committee’s knowledge of the availability and the feasibility of using other tissue sources such as hair. This is especially an issue in the case of pediatric disorders where the parent or guardian provides informed consent. The recent reports that iPSCs can be successfully derived from cells collected from human urine [2–5] could potentially address the aforementioned problems and greatly expand the number of patient-specific stem cells available to the research community. The few thousand epithelial-like cells harvested by centrifugation from a 50–250-ml sample of urine have been used as a source of iPSCs (UiPSCs) and neural progenitors (UiNPCs) [2–5]. UiPSCs, which have been generated using standard reprogramming factors, show the markers of pluripotency that are typical of iPSCs produced from other somatic cell types. UiPSCs can also be differentiated into at least three different lineages: hepatocytes, neurons and cardiomyocytes [5], and disease-specific UiPSCs have been generated for systemic lupus erythematosus [2]. It is also reported that UiNPCs can be reprogrammed directly from the urine epithelial-like cells using episomal vectors that, in contrast to retroand lenti-viruses, do not integrate into the genome [3]. It is further observed that the UiNPCs have the capacity to self-renew and can be differentiated into different types of functional neurons in vitro, and in vivo upon transplant into newborn rat brain. There is no question that urine offers benefits over dermal fibroblasts and most other tissues in terms of ease of collection and institutional study approval. The investigations of other groups will confirm whether UiPSCs are similar to standard iPSCs with respect to efficiency of reprogramming as well as degree of pluripotency and capacity for multilineage differentiation. Should this prove to be the case, UiPSCs The discovery that pluripotent stem cells can be induced by exposure of somatic cells to reprogramming factors has proven to be one of the most surprising and potentially useful discoveries in regenerative biology [1]. Patient-specific induced pluripotent stem cells (iPSCs) are being widely used to study disease mechanisms and to screen for novel drug therapies for a variety of human disorders. Fibroblasts were the first somatic cell type to be used in the successful generation of iPSCs and remain in widespread use despite the demonstration that iPSCs can be derived from other readily accessible sources, such as peripheral and cord blood, melanocytes, amniotic and periodontal tissue and hair follicle keratinocytes. The continued popularity of fibroblasts as a source of iPSCs may be historical in the sense that many laboratories began deriving fibroblasts from skin biopsies in anticipation of generating iPSCs and are now in the process of characterizing the disease-specific iPSC lines.