The erythroid phenotype of EKLF-null mice: Defects in hemoglobin metabolism and membrane stability
The erythroid phenotype of EKLF-null mice: Defects in hemoglobin metabolism and membrane stability
复制标题
DOI：
10.1128/mcb.25.12.5205-5214.2005
复制
发表时间：
2005-06-01
影响因子：
5.3
通讯作者：
Philipsen, S
中科院分区：
文献类型：
--
作者：
Drissen, R;von Lindern, M;Philipsen, S
红细胞的发育需要正确调节细胞过程，包括细胞形态、球蛋白表达和血红素合成的变化。红细胞Kruppel样因子EKLF（Klf 1）等转录因子在红细胞生成中发挥着关键作用。缺乏EKLF的小鼠在胚胎第14天左右死亡，原因是有缺陷的永久性红细胞生成，部分原因是P-珠蛋白表达不足。为了鉴定额外的靶基因，我们分析了在体外同步分化的野生型和EKLF无效的初级红系祖细胞的表型和基因表达谱。我们表明，EKLF是扩展的红系祖细胞，但所需的最后步骤的红系分化。我们确定EKLF依赖的基因参与血红蛋白代谢和膜稳定性。引人注目的是，这些基因的表达也是EKLF依赖于原始的，卵黄囊衍生的血细胞。与缺乏这些基因的上调一致，我们发现以前未检测到的形态异常EKLF无效的原始细胞。我们的数据提供了一个解释，迄今无法解释的严重性EKLF空表型在红细胞生成。
Development of red blood cells requires the correct regulation of cellular processes including changes in cell morphology, globin expression and heme synthesis. Transcription factors such as erythroid Kruppel-like factor EKLF (Klf1) play a critical role in erythropoiesis. Mice lacking EKLF die around embryonic day 14 because of defective definitive erythropoiesis, partly caused by a deficit in P-globin expression. To identify additional target genes, we analyzed the phenotype and gene expression profiles of wild-type and EKLF null primary erythroid progenitors that were differentiated synchronously in vitro. We show that EKLF is dispensable for expansion of erythroid progenitors, but required for the last steps of erythroid differentiation. We identify EKLF-dependent genes involved in hemoglobin metabolism and membrane stability. Strikingly, expression of these genes is also EKLF-dependent in primitive, yolk sac-derived, blood cells. Consistent with lack of upregulation of these genes we find previously undetected morphological abnormalities in EKLF-null primitive cells. Our data provide an explanation for the hitherto unexplained severity of the EKLF null phenotype in erythropoiesis.