Institute for Immunology, Faculty of Medicine, TU Dresden, Fetscherstrasse 74, 01307 Dresden, Germany.
Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center Utrecht, 3584 CT Utrecht, the Netherlands.
Stem Cell Reports. 2017 Jun 6;8(6):1472-1478. doi: 10.1016/j.stemcr.2017.04.012. Epub 2017 May 11.
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-1) identifies not only quiescent HSCs but quiescent cells on all hierarchical levels within the lineageSCA-1KIT (LSK) population. Each transplanted SCA-1 HSPC population also displayed self-renewal potential superior to that of the respective SCA-1 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.
血细胞的生成依赖于造血干细胞（HSC）和祖细胞群体的连续细胞输出，这些群体都包含静止和活跃循环的细胞。造血干细胞和祖细胞（HSPCs）表达表面分子 Stem cell antigen 1（SCA-1/LY6A）。利用组蛋白 2B-红色荧光融合蛋白标记保留和细胞周期报告小鼠，我们证明高 SCA-1 表达（SCA-1）不仅可以识别静止的 HSCs，还可以识别谱系 SCA-1KIT（LSK）群体中所有层次结构上的静止细胞。每个移植的 SCA-1 HSPC 群体也表现出优于相应 SCA-1 群体的自我更新潜力。SCA-1 表达可被 I 型干扰素（IFN）诱导。然而，我们表明，在稳态下具有更高 SCA-1 表达的细胞的静止和高自我更新能力与 I 型 IFN 信号无关。我们得出结论，SCA-1 表达水平可用于前瞻性分离功能异质性的 HSPC 亚群。
