SCA-1 Expression Level Identifies Quiescent Hematopoietic Stem and Progenitor Cells

Mina N F Morcos, Kristina B Schoedel, Anja Hoppe, Rayk Behrendt, Onur Basak, Hans C Clevers, Axel Roers, Alexander Gerbaulet

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgaveArtikelWetenschappelijkpeer review

Samenvatting

Blood cell generation depends on continuous cellular output by the sequential hierarchy of hematopoietic stem cell (HSC) and progenitor populations that all contain quiescent and actively cycling cells. Hematopoietic stem and progenitor cells (HSPCs) express the surface molecule Stem cell antigen 1 (SCA-1/LY6A). Using histone 2B-red fluorescent fusion protein label retention and cell-cycle reporter mice, we demonstrate that high SCA-1 expression (SCA-1hi) identifies not only quiescent HSCs but quiescent cells on all hierarchical levels within the lineage-SCA-1+KIT+ (LSK) population. Each transplanted SCA-1hi HSPC population also displayed self-renewal potential superior to that of the respective SCA-1lo population. SCA-1 expression is inducible by type I interferon (IFN). We show, however, that quiescence and high self-renewal capacity of cells with brighter SCA-1 expression at steady state were independent of type I IFN signaling. We conclude that SCA-1 expression levels can be used to prospectively isolate functionally heterogeneous HSPC subpopulations.

Originele taal-2Engels
Pagina's (van-tot)1472-1478
Aantal pagina's7
TijdschriftStem Cell Reports
Volume8
Nummer van het tijdschrift6
DOI's
StatusGepubliceerd - 06 jun 2017

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