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

• Orginal Article • Previous Articles     Next Articles

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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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