Broxmeyer Hal E, Cooper Scott, Lasky Laurence A, De Sauvage Frederic
Department of Microbiology and Immunology, Walther Oncology Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Stem Cells Dev. 2005 Apr;14(2):105-10. doi: 10.1089/scd.2005.14.105.
Previous studies have demonstrated that mice null (-/-) for either CD34 or c-mpl are viable and have greatly decreased numbers of multipotential (CFU-Mix), erythroid (BFU-E), and granulocytemacrophage (CFU-GM) progenitor cells in the bone marrow (BM), spleen (Spl) and peripheral blood (PB), without noticeable decreases in the nucleated cellularity of these organs. To evaluate the significance of these two proteins further, mice null for both CD34 and c-mpl were assessed for hematopoietic progenitor cells (HPC) and nucleated cellularity and compared with these cells in CD34-/- and c-mpl-/- mice. The following progenitors were assessed: CFU-GM, BFU-E, CFU-Mix with an erythroid component, CFU-Mix with erythroid and megakaryocyte components, nonerythroid CFU with a megakaryocyte (Meg) component and pure CFU-Meg. Results demonstrated significant decreases in progenitors in the BM of dual CD34/c-mpl-/- mice compared to decreases from CD34-/- or c-mpl-/- mice; progenitor numbers in CD34/c-mpl-/- mice were decreased by 83-99.3% compared to that in wild-type littermate control mice. Decreases in progenitors in spleens of c-mpl-/- mice (89-96%) were more drastic than those of CD34-/- mice (50-78%) whereas those of dual CD34/c-mpl-/- mice were equal to or lower than that of c-mpl-/- mice (93-98%). Decreases in PB progenitors were seen in the c-mpl-/- and dual CD34/c-mpl-/- mice (75-90%). Whereas progenitor cells in BM, Spl and PB were drastically reduced in dual CD34/c-mpl-/- mice compared to controls, absolute numbers of nucleated cells in these organs were essentially not reduced. These studies demonstrate that CD34 and c-mpl have non-redundant effects on maintenance of steady-state hematopoiesis and highlight how few progenitor cells are required in steady-state conditions to populate and maintain the BM, Spl, and PB with nucleated cells.
先前的研究表明，CD34或c-mpl基因敲除（-/-）的小鼠能够存活，其骨髓（BM）、脾脏（Spl）和外周血（PB）中的多能（CFU-Mix）、红系（BFU-E）和粒巨噬系（CFU-GM）祖细胞数量大幅减少，而这些器官中有核细胞数并未显著减少。为了进一步评估这两种蛋白的重要性，对CD34和c-mpl双基因敲除的小鼠的造血祖细胞（HPC）和有核细胞数进行了评估，并与CD34-/-和c-mpl-/-小鼠的这些细胞进行比较。评估了以下祖细胞：CFU-GM、BFU-E、含红系成分的CFU-Mix、含红系和巨核系成分的CFU-Mix、含巨核细胞（Meg）成分的非红系CFU和纯CFU-Meg。结果表明，与CD34-/-或c-mpl-/-小鼠相比，双基因敲除CD34/c-mpl-/-小鼠骨髓中的祖细胞显著减少；与野生型同窝对照小鼠相比，CD34/c-mpl-/-小鼠的祖细胞数量减少了83%-99.3%。c-mpl-/-小鼠脾脏中的祖细胞减少（89%-96%）比CD34-/-小鼠（50%-78%）更显著，而双基因敲除CD34/c-mpl-/-小鼠的祖细胞减少程度与c-mpl-/-小鼠相当或更低（93%-98%）。c-mpl-/-和双基因敲除CD34/c-mpl-/-小鼠的外周血祖细胞减少（75%-90%）。与对照相比，双基因敲除CD34/c-mpl-/-小鼠的骨髓、脾脏和外周血中的祖细胞显著减少，而这些器官中有核细胞的绝对数量基本未减少。这些研究表明，CD34和c-mpl在维持稳态造血方面具有非冗余作用，并突出了在稳态条件下，填充和维持骨髓、脾脏和外周血中有核细胞所需的祖细胞数量极少。
