title: Hematopoietic stem cells exhibit a specific ABC transporter gene expression profile clearly distinct from other stem cells.
abstract: BACKGROUND
  ATP-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.
  
  
  RESULTS
  ABC 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.
  
  
  CONCLUSIONS
  These 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.
authors.affiliation: Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Nijmegen Medical Centre/Nijmegen Centre for Molecular Life Sciences, Geert Grooteplein 8, 6525GA Nijmegen, The Netherlands.
authors.forename: Leilei
authors.initials: L
authors.lastname: Tang
authors.forename: Saskia M
authors.initials: SM
authors.lastname: Bergevoet
authors.forename: Christian
authors.initials: C
authors.lastname: Gilissen
authors.forename: Theo
authors.initials: T
authors.lastname: de Witte
authors.forename: Joop H
authors.initials: JH
authors.lastname: Jansen
authors.forename: Bert A
authors.initials: BA
authors.lastname: van der Reijden
authors.forename: Reinier A P
authors.initials: RA
authors.lastname: Raymakers
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D000273:Adipose Tissue / Q000166:cytology; D000328:Adult; D001773:Blood Cells / Q000166:cytology / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D005312:Fetal Blood / Q000166:cytology; D005434:Flow Cytometry; D015870:Gene Expression; D020869:Gene Expression Profiling; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D010012:Osteogenesis; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000378:metabolism*
chemical_list: D018528:ATP-Binding Cassette Transporters; D012333:RNA, Messenger