TGIF1在红细胞分化中的功能和机制研究

发布时间：2018-06-01 02:19

本文选题：红系分化 + TGIF　；参考：《发育医学电子杂志》2016年04期

【摘要】：目的筛选潜在的促红系分化因子,并验证其对红系分化的促进作用,探讨促分化机制。方法首先通过对高通量组学测序数据的分析,找到潜在红系调控转录因子;之后在红系分化的细胞模型TF-1细胞系中干扰该因子的表达,观察该因子的异常表达对红系分化的影响;进一步对目的基因敲低的细胞系进行转录组测序,同时利用生物信息学的手段分析受影响的红系相关因子以及通路。结果高通量组学测序分析得到潜在促红系分化调控因子TGIF1。TGIF1敲低细胞中,ε-珠蛋白、γ-珠蛋白、红系特异转录因子(GATA1、KLF1)、以及红系细胞表面特异糖蛋白标志分子CD235a的m RNA表达量及血红蛋白浓度均低于对照组。TGIF1过表达细胞的γ-珠蛋白m RNA高于对照组;促红细胞生成素诱导3天后,TGIF1过表达细胞表面CD235a的表达高于空白细胞组。进一步对稳定敲低TGIF1的TF-1细胞系进行高通量转录组测序分析,发现Smad复合物和相关靶基因表达上调,而GATA1和ALAS2的表达量则降低。结论 TGIF1是一个促红系分化的转录调控因子,可能通过影响转化生长因子β(transforming growth factor-β,TGFβ)通路中Smad复合物和相关靶基因的表达,或通过影响GATA1和ALAS2的表达来调控红系分化过程。
[Abstract]:Objective to screen the potential Erythroid differentiation factors (Erythroid differentiation factors) and to test their promoting effect on erythroid differentiation and to explore the mechanism of Erythroid differentiation. Methods by analyzing the high-throughput sequencing data, we found the potential erythroid regulatory transcription factor, and then interfered with the expression of the factor in the erythroid differentiation cell model TF-1 cell line. To observe the effect of abnormal expression of this factor on erythroid differentiation, to further sequence the target gene knockout cell lines, and to analyze the affected erythroid related factors and pathways by bioinformatics. Results 蔚 -globin and 纬 -globin were detected in TGIF1.TGIF1 knockout cells of potential erythroid differentiation regulators by high-throughput sequencing. The expression of m RNA and hemoglobin concentration of erythroid specific transcription factor GATA1C KLF1and erythroid cell surface specific glycoprotein marker CD235a were lower than those of the control group. The expression of 纬 -globin m RNA in the over-expressed cells was higher than that in the control group. After 3 days of erythropoietin induction, the expression of CD235a on the surface of TGIF1 overexpression cells was higher than that of blank cells. The high throughput transcriptome sequencing analysis of TF-1 cell lines with stable knockout TGIF1 revealed that the expression of Smad complex and related target genes was up-regulated while the expression of GATA1 and ALAS2 was decreased. Conclusion TGIF1 is a transcriptional regulator of erythroid differentiation. It may affect the expression of Smad complex and related target genes in transforming growth factor 尾 -transforming growth factor- 尾 (TGF- 尾) pathway, or regulate the process of erythroid differentiation by affecting the expression of GATA1 and ALAS2.
【作者单位】：中国科学院北京基因组研究所中国科学院基因组学与信息重点实验室;中国科学院大学生命科学学院;中国科学院大学中丹学院;
【基金】：国家自然科学基金(31471115、31401160、81670109)
【分类号】：R331

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