The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia.
Immunity. 2010 May 28;32(5):628-41. doi: 10.1016/j.immuni.2010.05.005.
The transcription factor PU.1 plays multiple context and concentration dependent roles in lymphoid and myeloid cell development. Here we showed that PU.1 (encoded by Sfpi1) was essential for dendritic cell (DC) development in vivo and that conditional ablation of PU.1 in defined precursors, including the common DC progenitor, blocked Flt3 ligand-induced DC generation in vitro. PU.1 was also required for the parallel granulocyte-macrophage colony stimulating factor-induced DC pathway from early hematopoietic progenitors. Molecular studies demonstrated that PU.1 directly regulated Flt3 in a concentration-dependent manner, as Sfpi1(+/-) cells displayed reduced expression of Flt3 and impaired DC formation. These studies identify PU.1 as a critical regulator of both conventional and plasmacytoid DC development and provide one mechanism how altered PU.1 concentration can have profound functional consequences for hematopoietic cell development.
转录因子 PU.1 在淋巴样和髓样细胞发育中发挥多种依赖上下文和浓度的作用。在这里，我们表明 PU.1（由 Sfpi1 编码）对于体内树突状细胞（DC）的发育是必需的，并且在定义的前体（包括普通 DC 祖细胞）中条件性缺失 PU.1 会阻止 Flt3 配体诱导的 DC 在体外生成。PU.1 对于来自早期造血祖细胞的平行粒细胞-巨噬细胞集落刺激因子诱导的 DC 途径也是必需的。分子研究表明，PU.1 以浓度依赖的方式直接调节 Flt3，因为 Sfpi1(+/-)细胞显示出 Flt3 表达减少和 DC 形成受损。这些研究确定了 PU.1 是常规和浆细胞样 DC 发育的关键调节剂，并提供了一种机制，即改变 PU.1 浓度如何对造血细胞发育产生深远的功能影响。
