Signal transducer and activator of transcription 5a (STAT5a) is required for eosinophil differentiation of human cord blood-derived CD34+ cells
Signal transducer and activator of transcription 5a (STAT5a) is required for eosinophil differentiation of human cord blood-derived CD34+ cells
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DOI：
10.1182/blood-2002-03-0740
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发表时间：
2003-01-01
期刊：
影响因子：
20.3
通讯作者：
Koenderman, L
中科院分区：
文献类型：
--
作者：
Buitenhuis, M;Baltus, B;Koenderman, L
已报道信号转导子和转录激活子（STATs）在几种骨髓细胞系的分化中起关键作用，尽管STATs在原代人造血细胞分化中的重要性仍有待确定。终末嗜酸性粒细胞分化由白细胞介素-5（IL-5）诱导，其也已被证明激活STAT 5。我们已经研究了STAT 5是否在使用脐带血来源的CD 34（+）细胞的嗜酸性粒细胞分化过程中起关键作用。在该离体系统中，STAT 5表达和活化在分化早期是高的，并且STAT 5蛋白表达在嗜酸性粒细胞分化的最后阶段被下调。进行逆转录病毒转导以在CD 34（+）细胞中异位表达野生型和显性阴性STAT 5a（STAT 5aDelta 750）。与仅用空载体转导的细胞相比，用STAT 5a转导的细胞导致增强的增殖。有趣的是，STAT 5a的异位表达也导致加速分化。相反，STAT 5aDelta 750的异位表达在分化中重新适合于阻断，而增殖也被严重抑制。用显性阴性STAT 5 b获得了类似的结果。STAT 5a的强制表达增强了STATS靶基因Bcl-2和p21（WAF/ClP 1）的表达，表明它们可能在STMa介导的嗜酸性粒细胞分化中很重要。这些结果表明STAT 5在原代人造血细胞的嗜酸性粒细胞分化中起关键作用。(C)2003年，美国血液学会。
Signal transducers and activators of transcription (STATs) have been reported to play a critical role in the differentiation of several myelold cell lines, although the importance of STATS In the differentiation of primary human hematopoietic cells remains to be established. Terminal eosinophil differentiation is induced by interleukin-5 (IL-5), which has also been demonstrated to activate STAT5. We have investigated whether STAT5 plays a critical role during eosinophil differentiation using umbilical cord blood-derived CD34(+) cells. In this ex vivo system, STAT5 expression and activation are high early during differentiation, and STAT5 protein expression is down-regulated during the final stages of eosinophil differentiation. Retroviral transductions were performed to ectopically express wild-type and dominant-negative STAT5a (STAT5aDelta750) in CD34(+) cells. Transduction of cells with STAT5a resulted in enhanced proliferation compared with cells transduced with empty vector alone. Interestingly, ectopic expression of STAT5a also resulted in accelerated differentiation. In contrast, ectopic expression of STAT5aDelta750 re-suited in a block in differentiation, whereas proliferation was also severely inhibited. Similar results were obtained with dominant-negative STAT5b. Forced expression of STAT5a enhanced expression of the STATS target genes Bcl-2 and p21(WAF/ClP1), suggesting they may be important in STMa-mediated eosinophil differentiation. These results demonstrate that STAT5 plays a critical role in eosinophil differentiation of primary human hematopoietic cells. (C) 2003 by The American Society of Hematology.