WNT signaling modulates the diversification of hematopoietic cells
WNT signaling modulates the diversification of hematopoietic cells
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DOI：
10.1182/blood.v96.13.4132.h8004132_4132_4141
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发表时间：
2000-12-15
期刊：
影响因子：
20.3
通讯作者：
Eisenberg, CA
中科院分区：
文献类型：
--
作者：
Brandon, C;Eisenberg, LM;Eisenberg, CA
WNT蛋白是一个调节细胞命运和行为的分泌信号分子家族。研究了wnt对造血细胞命运的可能影响。利用造血祖细胞（HPC）富集的禽类胚胎骨髓细胞和鹌鹑中胚层干细胞QCE6进行研究。在优化条件下，骨髓细胞和QCE6细胞表现一致，并发育为红细胞（rbc）、单核细胞、巨噬细胞、粒细胞和血小板。QCE6细胞表现出的这种广泛的血细胞表型依赖于它们对WNT11的活性表达。然而，当通过表达稳定转染的WNT11反义基因来阻止QCE6细胞产生WNT11时，培养物以高度空泡化的巨噬细胞为主。这些培养中红细胞缺失，单核细胞的存在也大大减少。将这些WNT11反义细胞暴露于可溶性WNT11或WNT5a中，可以恢复亲代QCE6细胞所表现出的广泛的血细胞表型。WNT蛋白在QCE6细胞中的过表达进一步增加了红细胞和单核细胞的患病率，并大大减少了巨噬细胞的外观。因此，用可溶性WNT11或WNT5a处理富含hpc的骨髓培养物可抑制巨噬细胞的形成。相反，单核细胞和红细胞是wnt处理的骨髓培养中显示的普遍细胞。综上所述，这些数据表明wnt可能在调节造血细胞命运中发挥重要作用。(C) 2000年由美国血液学会出版。
WNT proteins compose a family of secreted signaling molecules that regulate cell fate and behavior. The possible influence of WNTs on hematopoietic cell fate was examined. Both hematopoietic progenitor cell (HPC)-enriched embryonic avian bone marrow cells and the quail mesodermal stem cell line QCE6 were used for these studies. Under optimized conditions, the bone marrow and QCE6 cells behaved identically and developed into red blood cells (RBCs), monocytes, macrophages, granulocytes, and thrombocytes. This broad range of blood cell phenotypes exhibited by QCE6 cells was dependent on their active expression of WNT11. However, when QCE6 cells were prevented from producing WNT11-by expression of a stably transfected WNT11 antisense transgene-the cultures were dominated by highly vacuolated macrophages. RBCs were absent from these cultures, and the presence of monocytes was greatly diminished. Exposure of these WNT11 antisense cells to soluble WNT11 or WNT5a restored the broad range of blood cell phenotypes exhibited by parental QCE6 cells. Overexpression of WNT protein in QCE6 cells further increased the prevalence of RBCs and monocytes and greatly diminished the appearance of macrophages. Accordingly, treatment of HPC-enriched bone marrow cultures with soluble WNT11 or WNT5a inhibited macrophage formation. Instead, monocytes and RBCs were the prevalent cells displayed by WNT-treated bone marrow cultures. Together, these data Indicate that WNTs may play a major role in regulating hematopoietic cell fate. (C) 2000 by The American Society of Hematology.