Deletion of Dicer in late erythroid cells results in impaired stress erythropoiesis in mice.

Deletion of Dicer in late erythroid cells results in impaired stress erythropoiesis in mice.
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DOI:
10.1016/j.exphem.2014.06.004
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发表时间:
2014-10
影响因子:
2.6
通讯作者:
Papayannopoulou, Thalia
Papayannopoulou, Thalia
中科院分区:
医学4区
文献类型:
--
作者:
Byon, John C. H.;Padilla, Steven M.;Papayannopoulou, Thalia

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MicroRNAs (miRNAs)已被证明影响红系谱系的承诺和分化。然而,我们对miRNA在终末红细胞生成中的功能的了解仍然有限。为了解决这个问题,我们建立了一个新的动物模型,其中mirna加工酶Dicer在促红细胞生成素受体阳性的红细胞中选择性失活,从CFU-e/原红细胞开始。这导致从原红细胞阶段开始的所有mirna的显著消耗,只有一个例外,miR-451,它被Ago2以一种与dicer无关的方式加工。我们观察到成熟的dicer依赖性mirna,如miR-451,在稳态条件下是必不可少的,但这些突变体对应激性红细胞生成的反应受损,这可以通过贫血恢复延迟来证明。这种缺陷是成熟较晚的红细胞所特有的,因为祖细胞数量不受影响。除了建立一个新的小鼠模型来研究miRNA在晚红细胞中的功能外,我们还得出结论,miRNA(包括dicer依赖性和独立型)主要调节晚红细胞对应激的最佳反应。
MicroRNAs (miRNAs) have been shown to influence erythroid lineage commitment and differentiation. However, our knowledge of miRNA function in terminal erythropoiesis remains limited. To address this issue, we generated a novel animal model, where the miRNA-processing enzyme, Dicer, is selectively inactivated in erythropoietin receptor positive erythroid cells beginning with CFU-e/proerythroblast cells. This results in significant depletion of all miRNAs from the proerythroblast stage onwards, with one exception, miR-451, which is processed by Ago2 in a Dicer-independent manner. We observed that mature Dicer-dependent miRNAs, like miR-451, are dispensable under steady-state conditions, but these mutants have an impaired response to stress erythropoiesis, as demonstrated by a delay in recovery from anemia. This defect was specific to later maturing erythroid cells, as progenitor numbers were unaffected. In addition to generating a novel mouse model to study miRNA function in late erythroid cells, we conclude that miRNAs (both Dicer-dependent and independent) act primarily to regulate the optimal response to stress among late erythroid cells.
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