class="head no_bottom_margin" id="sec1title">IntroductionThe multi-potent and self-renewing hematopoietic stem cells (HSCs) at the top of the hierarchy give rise to hematopoietic progenitor cell (HPC) populations with gradually narrowing differentiation and self-renewal potential (). Murine HSCs and uncommitted progenitors express the glycosyl phosphatidylinositol-anchored cell surface protein Stem cell antigen 1 (SCA-1/LY6A) () and reside within the lineage−SCA-1+KIT+ (LSK) population (, , ) of the bone marrow (BM).Numerous studies have demonstrated heterogeneity within each of the hematopoietic stem and progenitor cell (HSPC) populations with regard to cell-cycle activity (), lineage specification (, ), and repopulation activity (, ). Multiple cell-surface markers allowing for prospective isolation of the quiescent subset of HSCs (, , , , , href="#bib29" rid="bib29" class=" bibr popnode">Sudo et al., 2012) have been proposed. However, a marker uniformly associated with quiescence among the LSK population has been lacking so far. Two recent studies (href="#bib25" rid="bib25" class=" bibr popnode">Säwén et al., 2016, href="#bib35" rid="bib35" class=" bibr popnode">Wilson et al., 2015) showed increased quiescence and repopulation activity of immunophenotypic HSCs with high expression of SCA-1 (SCA-1hi).While the function of the SCA-1 molecule remains enigmatic (href="#bib13" rid="bib13" class=" bibr popnode">Holmes and Stanford, 2007), it is well established that SCA-1 is strongly upregulated by type I (href="#bib9" rid="bib9" class=" bibr popnode">Essers et al., 2009, href="#bib21" rid="bib21" class=" bibr popnode">Pietras et al., 2014) and type II (href="#bib5" rid="bib5" class=" bibr popnode">de Bruin et al., 2014) interferon (IFN). SCA-1 seems to regulate cellular responses to type I IFN as loss of SCA-1 abrogates type I IFN-induced proliferation of HSCs (href="#bib9" rid="bib9" class=" bibr popnode">Essers et al., 2009, href="#bib32" rid="bib32" class=" bibr popnode">Walter et al., 2015).In the present work, we show that type I IFN-independent high expression of SCA-1 identifies quiescent cells with elevated repopulation activity not only in the HSC compartment but also in LSK progenitor populations.
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