遗传 ›› 2018, Vol. 40 ›› Issue (11): 998-1006.doi: 10.16288/j.yczz.18-174

• 研究报告 • 上一篇    下一篇

KLF1和KLF9对K562细胞红系分化的协同调控作用

任岚1,2,肖茹丹1,2,张倩1,2,娄晓敏1,3,张昭军1,3,4,方向东1,2,3,4()   

  1. 1. 中国科学院北京基因组研究所,中国科学院基因组科学与信息重点实验室,北京 100101
    2. 中国科学院大学生命科学学院,北京 100049
    3. 中国科学院大学中丹学院,北京 101408
    4. 中国科学院干细胞与再生创新研究院,北京 100190
  • 收稿日期:2018-06-29 修回日期:2018-09-30 出版日期:2018-11-20 发布日期:2018-10-24
  • 通讯作者: 方向东 E-mail:fangxd@big.ac.cn
  • 作者简介:任岚,硕士研究生,专业方向：疾病组学与转化医学研究。E-mail: eico. renlan@gmail.com|肖茹丹,硕士研究生,专业方向：疾病组学与转化医学研究。E-mail: xiaorudan@big.ac.cn,任岚和肖茹丹并列第一作者。
  • 基金资助:
    中国科学院器官重建与制造战略性先导科技专项(XDA16010200);国家自然科学基金项目(81700097);国家自然科学基金项目(81700116);国家自然科学基金项目(81670109);国家自然科学基金项目(31471115);国家自然科学基金项目(31371300)

Synergistic regulation of the erythroid differentiation of K562 cells by KLF1 and KLF9

Lan Ren1,2,Rudan Xiao1,2,Qian Zhang1,2,Xiaomin Lou1,3,Zhaojun Zhang1,3,4,Xiangdong Fang1,2,3,4()   

  1. 1. CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China
    2. Life Sciences College,University of Chinese Academy of Sciences, Beijing 100049, China
    3. Sion-Danish College, University of Chinese Academy of Sciences, Beijing 101408, China
    4. Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China
  • Received:2018-06-29 Revised:2018-09-30 Online:2018-11-20 Published:2018-10-24
  • Contact: Fang Xiangdong E-mail:fangxd@big.ac.cn
  • Supported by:
    Supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16010200);the National Natural Science Foundation of China(81700097);the National Natural Science Foundation of China(81700116);the National Natural Science Foundation of China(81670109);the National Natural Science Foundation of China(31471115);the National Natural Science Foundation of China(31371300)

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摘要：

Krüppel样因子(Krüppel-like factors,KLFs)是锌指蛋白超家族的一个亚家族,参与细胞内的多种生理、病理过程,该家族成员在红细胞分化发育过程中发挥非常重要的作用,但是家族成员间对红系分化的协同调控作用还鲜有报道。本课题组前期研究发现,KIF家族成员KLF1和KLF9在已分化的红系细胞中的表达水平显著高于造血干细胞。为进一步探讨二者在红系分化中是否存在协同作用,本研究在K562细胞中分别过表达/敲低表达KLF1和KLF9,检测二者表达的相关性,发现KLF1和KLF9的基因表达呈现正相关,且二者共表达可以显著促进K562细胞红系分化,特异地增强β-珠蛋白的表达。通过对KLF1、KLF9单独和共同过表达、敲低表达的K562细胞转录组数据的分析发现二者可能通过PI3K-Akt和FoxO通路协同调控红系分化,FOS、TF、IL8是协同调控的候选靶基因。本研究结果为后续深入研究KLF1和KLF9协同调控红系分化的分子机制奠定了基础。

关键词: 红系分化, KLF, 转录组测序, 转录因子

Abstract:

Krüppel-like factors (KLFs) regulate diverse physiological processes such as the differentiation and development of red blood cells. However, it remains unclear whether KLFs exhibit synergistic regulatory effects. Transcriptomic data from our previous study showed that KLF1 and KLF9 expression was significantly higher in differentiated red blood cells than in hematopoietic stem cells. In the present study, we manipulated KLF1 and KLP9 gene expression by overexpressing or knocking down KLF1 and KLF9 in K562 cells and revealed a positive correlation between the expression of KLF1 and KLF9; their co-expression can significantly promote erythroid differentiation and specifically enhance β-globin gene expression. Further, we analyzed the transcriptome data of K562 cells with altered KLF1/KLF9 levels and found that KLF1 and KLF9 synergistically regulated erythroid differentiation through the PI3K-Akt and FoxO signaling pathways. KLF1 and KLF9 may exert this synergistic effect through FOS, TF, and IL8 in K562 cells. We have provided evidence that KLF1 and KLF9 play a synergistic role in regulating erythroid differentiation.

Key words: erythroid differentiation, KLF, transcriptome sequencing, transcription factors