Ikuta K, Ingolia D E, Friedman J, Heimfeld S, Weissman I L
Howard Hughes Medical Institute, Stanford, California.
Int J Cell Cloning. 1991 Sep;9(5):451-60. doi: 10.1002/stem.1991.5530090503.
Hematopoietic stem cells (HSCs) are distinguished from other hematopoietic progenitors in bone marrow by their unique ability to undergo multilineage differentiation and self-renewal. Two mouse mutations, dominant spotting (W) and steel (Sl), have pleiotropic effects on hematopoiesis, gametogenesis, and melanoblast development. These two mutations have been shown to be intrinsic (W) and microenvironmental (Sl) defects. Recently, molecular studies revealed that the W and Sl loci encode the c-kit receptor and steel factor (SLF), respectively. The c-kit receptor is expressed on HSCs and hematopoietic progenitors, while SLF is produced by stromal cells. SLF acts on hematopoietic progenitors synergistically with other growth factors. Here we review the effect of these mutations on mouse hematopoiesis, and show that SLF acts on HSCs and other myeloerythroid progenitors, but that it, in our hands, does not play a critical role in HSC generation or self-renewal. Rather, SLF is the most potent co-mitogen (with IL-1, IL-3, IL-6, G-CSF, GM-CSF, or M-CSF) found that acts on these cells, but the effect of such treatments is the rather specific and massive expansion of myeloerythropoiesis, not lymphopoiesis, and perhaps at the expense of HSC self-renewal.
造血干细胞（HSCs）与骨髓中的其他造血祖细胞不同，因其具有独特的多谱系分化和自我更新能力。两个小鼠突变，显性斑点（W）和钢（Sl），对造血、配子发生和黑素母细胞发育具有多效性影响。这两个突变已被证明分别是内在性（W）和微环境性（Sl）缺陷。最近，分子研究表明，W和Sl位点分别编码c-kit受体和钢因子（SLF）。c-kit受体在造血干细胞和造血祖细胞上表达，而SLF由基质细胞产生。SLF与其他生长因子协同作用于造血祖细胞。在这里，我们综述了这些突变对小鼠造血的影响，并表明SLF作用于造血干细胞和其他髓系红细胞祖细胞，但在我们的研究中，它在造血干细胞的产生或自我更新中并不起关键作用。相反，SLF是已发现的对这些细胞作用最强的共促分裂原（与白细胞介素-1、白细胞介素-3、白细胞介素-6、粒细胞集落刺激因子、粒细胞-巨噬细胞集落刺激因子或巨噬细胞集落刺激因子一起），但这种处理的效果是髓系红细胞生成的相当特异性和大量扩增，而非淋巴细胞生成，并且可能是以造血干细胞自我更新为代价。
