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

Stem Cell Reports
Mina N F MorcosAlexander Gerbaulet

Abstract

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-1hiHSPC population also displayed self-renewal potential superior to that of the respective SCA-1lopopulation. 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.

Citations

Jun 28, 2019·Journal of Cellular Biochemistry·Cixia LiZhikun Guo
Apr 18, 2020·The Journal of Experimental Medicine·Mina N F MorcosAlexander Gerbaulet
May 21, 2020·Frontiers in Immunology·Yafei DengXiaohui Li
Nov 6, 2020·The Journal of Clinical Investigation·Kartik SehgalDavid A Barbie

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Methods Mentioned

BETA
flow cytometry

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