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- Title
Dual SP/ALDH Functionalities Refine the Human Hematopoietic Lin-CD34+CD38- Stem/Progenitor Cell Compartment.
- Authors
PIERRE-LOUIS, OLIVIER; CLAY, DENIS; DE LA GRANGE, PHILIPPE BRUNET; BLAZSEK, ISTVAN; DESTERKE, CHRISTOPHE; GUERTON, BERNADETTE; BLONDEAU, CAMILLE; MALFUSON, JEAN-VALÈRE; PRAT, MARIE; ANNELISE BENNACEUR-GRISCELLI; LATILLADE, JEAN-JACQUES; LE BOUSSE-KERDILÈS, MARIE-CAROLINE
- Abstract
Identification of prevalent specific markers is crucial to stem/ progenitor cell purification. Determinants such as the surface antigens CD34 and CD38 are traditionally used to analyze and purify hematopoietic stem/progenitor cells (HSCs/HPCs). However, the variable expression of these membrane antigens poses some limitations to their use in HSC/HPC purification. Techniques based on drug/stain efflux through the ATP-binding cassette (ABC)G2 pump (side population [SP] phenotype) or on detection of aldehyde dehydrogenase (ALDH) activity have been independently developed and distinguish the SP and ALDHBrigfit (ALDHltr) cell subsets for their phenotype and pro- liferative capability. In this study, we developed a multipara- metric flow cytometric method associating both SP and ALDH activities on human lineage negative (Lin~) bone marrow cells and sorted different cell fractions according to their SP/ALDH activity level. We find that Lin~CD34+CD38Low/~ cells are found throughout the spectrum of ALDH expression and are enriched especially in ALDHBr cells when associated with SP functionality (SP/ALDHBr fraction). Furthermore, the SP marker identified Go cells in all ALDH fractions, allowing us to sort quiescent cells regardless of ALDH activity. Moreover, we show that, within the Lin~CD34+CD38~ALDHBr population, the SP marker identifies cells with higher primitive characteristics, in terms of sternness-related gene expression and in vitro and in vivo proliferative potential, than the Lin~CD34+ CD38~ALDH main population cells. In conclusion, our study shows that the coexpression of SP and ALDH markers refines the Lin~CD34+CD38~ hematopoietic compartment and identifies an SP/ALDHBr cell subset enriched in quiescent primitive HSCs/HPCs. Stem Cells 2009 ;27-.2552-2562
- Subjects
HEMATOPOIETIC stem cells; CELL surface antigens; ALDEHYDES; PHENOTYPES; BONE marrow cells
- Publication
Stem Cells, 2009, Vol 27, Issue 10, p2552
- ISSN
1066-5099
- Publication type
Article
- DOI
10.1002/stem.186