Ineffective erythropoiesis in Stat5a-/-5b-/- mice due to decreased survival of early erythroblasts
Ineffective erythropoiesis in Stat5a-/-5b-/- mice due to decreased survival of early erythroblasts
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DOI：
10.1182/blood.v98.12.3261
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发表时间：
2001-12-01
期刊：
影响因子：
20.3
通讯作者：
Lodish, HF
中科院分区：
文献类型：
--
作者：
Socolovsky, M;Nam, H;Lodish, HF
红细胞生成素（Epo）在基础状态和应激状态下控制红细胞的产生。在红系祖细胞上，Epo与其受体EpoR结合，导致转录因子Stat5的快速激活。先前，在Stat5a(-/-)5b（-/-）小鼠中发现胎儿贫血和胎儿肝红细胞祖细胞凋亡增加。然而，Stat5在成人红细胞生成中的作用尚不清楚。目前的研究表明，一些成年Stat5a(-/-)5b（-/-）小鼠具有接近正常的红细胞压积，但在应激反应中缺乏产生高的红细胞生成率。此外，许多成年Stat5a(-/-)5b（-/-）小鼠存在持续性贫血，尽管它们的红细胞组织有明显的代偿性扩张。对Stat5a(-/-)5b（-/-）造血组织中红母细胞成熟的分析显示，早期红母细胞数量显著增加，但它们在分化过程中没有进展。Stat5a(-/-)5b（-/-）早期红母细胞中bcl-(XL)表达降低和细胞凋亡增加与贫血程度相关。因此，Stat5控制着早期红母细胞存活的速率决定步骤。[血液。2001;98:3261-3273](C) 2001由美国血液学会。
Erythropoietin (Epo) controls red cell production in the basal state and during stress. Epo binding to its receptor, EpoR, on erythroid progenitors leads to rapid activation of the transcription factor Stat5. Previously, fetal anemia and increased apoptosis of fetal liver erythroid progenitors were found in Stat5a(-/-)5b(-/-) mice. However, the role of Stat5 in adult erythropoiesis was not clear. The present study shows that some adult Stat5a(-/-)5b(-/-) mice have a near-normal hematocrit but are deficient in generating high erythropoletic rates in response to stress. Further, many adult Stat5a(-/-)5b(-/-) mice have persistent anemia despite a marked compensatory expansion in their erythropoletic tissue. Analysis of erythroblast maturation in Stat5a(-/-)5b(-/-) hematopoletic tissue shows a dramatic increase in early erythroblast numbers, but these fail to progress in differentiation. Decreased expression of bcl-(XL) and increased apoptosis in Stat5a(-/-)5b(-/-) early erythroblasts correlate with the degree of anemia. Hence, Stat5 controls a rate-determining step regulating early erythroblast survival. (Blood. 2001;98:3261-3273) (C) 2001 by The American Society of Hematology.