Abstract
BackgroundATP-binding cassette (ABC) transporters protect cells against unrelated (toxic) substances by pumping them across cell membranes. Earlier we showed that many ABC transporters are highly expressed in hematopoietic stem cells (HSCs) compared to more committed progenitor cells. The ABC transporter expression signature may guarantee lifelong protection of HSCs but may also preserve stem cell integrity by extrusion of agents that trigger their differentiation. Here we have studied whether non-hematopoietic stem cells (non-HSCs) exhibit a similar ABC transporter expression signature as HSCs.ResultsABC transporter expression profiles were determined in non-hematopoietic stem cells (non-HSCs) from embryonic, neonatal and adult origin as well as in various mature blood cell types. Over 11,000 individual ABC transporter expression values were generated by Taqman Low Density Arrays (TLDA) to obtain a sensitivity comparable with quantitative real-time polymerase chain reactions. We found that the vast majority of transporters are significantly higher expressed in HSCs compared to non-HSCs. Furthermore, regardless their origin, non-HSCs exhibited strikingly similar ABC transporter expression profiles that were distinct from those in HSCs. Yet, sets of transporters characteristic for different stem cell types could be identified, suggesting restricted functions in stem cell physiology. Remarkably, in HSCs we could not pinpoint any single transporter expressed at an evidently elevated level when compared to all the mature blood cell types studied.ConclusionsThese findings challenge the concept that individual ABC transporters are implicated in maintaining stem cell integrity. Instead, a distinct ABC transporter expression signature may be essential for stem cell function. The high expression of specific transporters in non-HSCs and mature blood cells suggests a specialized, cell type dependent function and warrants further functional experiments to determine their exact roles in cellular (patho)physiology.
Highlights
ATP-binding cassette (ABC) transporters protect cells against unrelated substances by pumping them across cell membranes
In this study we aimed to investigate whether other non-related stem cells exert a similar ABC transporter signature as hematopoietic stem cells (HSCs) and profiled transporter expression in human non-HSCs including unrestricted somatic stem cells (USSCs), mesenchymal stem cells (MSCs), embryonic stem cells (ESCs) and multipotent adult progenitor cells (MAPCs)
Non-HSCs show striking similarities in ABC transporter expression profiles clearly distinct from HSCs Earlier we showed that a broad range of ABC transporters was highly expressed in HSCs compared to more committed progenitor cells [13]
Summary
ATP-binding cassette (ABC) transporters protect cells against unrelated (toxic) substances by pumping them across cell membranes. The ABC transporter expression signature may guarantee lifelong protection of HSCs but may preserve stem cell integrity by extrusion of agents that trigger their differentiation. We have studied whether non-hematopoietic stem cells (non-HSCs) exhibit a similar ABC transporter expression signature as HSCs. Controversy has lasted for years regarding the role of ATP-binding cassette (ABC) transporters in (cancer) stem cell integrity [1,2,3,4,5,6,7,8]. SP fractions have been that show a significantly lower expression level of ABCB1 and ABCG1 [13] have no repopulating capacities [5,14] These findings could suggest that ABC transporters contribute to maintain stem cell properties of both normal and cancer stem cells. As the human gene encodes for 49 ABC transporters, functional redundancy may preserve stem cell integrity and chemoresistance following abrogation of the function of one or several transporters
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