Zfat对胎儿肝脏中红细胞的发育至关重要。
Zfat Is Indispensable for the Development of Erythroid Cells in the Fetal Liver.
作者信息
Doi Keiko, Tsunoda Toshiyuki, Koyanagi Midori, Tanaka Yoko, Yamano Shiori, Fujikane Aya, Nishi Kensuke, Ishikura Shuhei, Shirasawa Senji
机构信息
Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan
Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka, Japan.
出版信息
Anticancer Res. 2019 Aug;39(8):4495-4502. doi: 10.21873/anticanres.13625.
BACKGROUND/AIM: In mice, fetal liver is the first tissue of definitive erythropoiesis for definitive erythroid expansion and maturation. ZFAT, originally identified as a candidate susceptibility gene for autoimmune thyroid disease, has been reported to be involved in primitive hematopoiesis and T cell development. The aim of this study was to examine whether or not Zfat is involved in definitive erythropoiesis in the fetal liver during mammalian development.
MATERIALS AND METHODS
The role of Zfat during mouse fetal erythropoiesis in the fetal liver was examined using tamoxifen-inducible CreERT2 Zfat-deficient mice.
RESULTS
Zfat-deficient mice exhibit moderate anemia with small and pale fetal liver through a decreased number of erythroblasts by E12.5. Apoptosis sensitivity in fetal liver erythroid progenitors was enhanced by Zfat-deficiency ex vivo. Moreover, Zfat knockdown partially inhibited CD71Ter119 to CD71Ter119 transition of fetal liver erythroid progenitors with impairment in the elevation of CD71 expression.
CONCLUSION
Zfat plays a critical role for erythropoiesis in the fetal liver.
背景/目的：在小鼠中，胎肝是确定性红细胞生成以实现确定性红系扩增和成熟的首个组织。ZFAT最初被鉴定为自身免疫性甲状腺疾病的候选易感基因，据报道其参与原始造血和T细胞发育。本研究的目的是检测在哺乳动物发育过程中ZFAT是否参与胎肝中的确定性红细胞生成。
材料与方法
使用他莫昔芬诱导型CreERT2 Zfat缺陷小鼠检测ZFAT在小鼠胎肝胎儿红细胞生成过程中的作用。
结果
到胚胎第12.5天，ZFAT缺陷小鼠因成红细胞数量减少而出现中度贫血，伴有小而苍白的胎肝。体外实验中，ZFAT缺陷增强了胎肝红系祖细胞的凋亡敏感性。此外，敲低ZFAT部分抑制了胎肝红系祖细胞从CD71Ter119到CD71Ter119的转变，同时CD71表达升高受损。
结论
ZFAT在胎肝红细胞生成中起关键作用。
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