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Signaling from Fibroblast Growth Factor Receptor 2 in Immature Hematopoietic Cells Facilitates Donor Hematopoiesis After Intra-Bone Marrow–Bone Marrow Transplantation

机译:骨髓内-骨髓移植后,未成熟造血细胞中成纤维细胞生长因子受体2的信号促进供体造血

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摘要

Fibroblast growth factor (FGF) and FGF receptor (FGFR) are expressed in various cells including endothelial progenitor cells and hematopoietic cells. The interaction between FGF and FGFR is associated with the proliferation, migration, and survival of these cells. In this report, we examined the effects of FGFR2 signaling on hematopoiesis in immature hematopoietic cells, using mutant mice in which a constitutively active form of FGFR2 mutant was caused to be overexpressed by the Tie2 promoter (FGFR2 Tg mice). Under normal conditions, hematopoiesis of FGFR2 Tg mice and wild type (Wt) mice do not differ significantly, except for the weight and cell numbers of the thymus. However, the c-kit+Sca-1+lineage− bone marrow cells (BMCs) of FGFR2 Tg mice facilitate the formation of colony-forming units of culture. When these BMCs were transplanted into the recipient bone marrow (intra-bone marrow–bone marrow transplantation), there was better reconstitution of donor hematopoietic cells. In the in vitro experiment, the c-kit+Sca-1+lineage− BMCs from FGFR2 Tg mice showed fewer apoptotic cells than those from Wt mice. These results suggest that the antiapoptotic effect of FGFR2 signaling facilitates the hematopoiesis of FGFR2 Tg mice.
机译:成纤维细胞生长因子(FGF)和FGF受体(FGFR)在包括内皮祖细胞和造血细胞在内的各种细胞中表达。 FGF和FGFR之间的相互作用与这些细胞的增殖,迁移和存活有关。在本报告中,我们使用突变小鼠(其中FGFR2突变体的组成型活性形式被Tie2启动子过度表达)检查了FGFR2信号对未成熟造血细胞中造血功能的影响(FGFR2 Tg小鼠)。在正常条件下,除了胸腺的重量和细胞数量外,FGFR2 Tg小鼠和野生型(Wt)小鼠的造血作用没有显着差异。但是,FGFR2 Tg小鼠的c-kit + Sca-1 +谱系-骨髓细胞(BMC)促进了培养菌落形成单位的形成。将这些BMC移植到受体骨髓中(骨髓内-骨髓移植)后,供体造血细胞的重建效果更好。在体外实验中,FGFR2 Tg小鼠的c-kit + Sca-1 + lineage- BMCs的凋亡细胞少于Wt小鼠的。这些结果表明,FGFR2信号传导的抗凋亡作用促进了FGFR2 Tg小鼠的造血作用。

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