Down-regulation of the Transcription Factor KLF4 Is Required for the Lineage Commitment of T cells

Mouse somatic cells can be reprogrammed into pluripotent stem cells by ectopic expression of the reprogramming factors Oct4, Sox2, c-Myc and Klf4, which are highly expressed in embryonic stem cells. Presumably, the expression of these genes, especially Oct4, Sox2 and Klf4 may be turned off or down-regulated during the differentiation of pluripotent cells into a variety of differentiated derivatives. However, the roles of the reprogramming factors in early T cell development are incompletely defined. Recently, a team of researchers, led by LIU Xiaolong, at the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, revealed that the down-regulation of Klf4 is required for T cell lineage commitment.

 

WEN Xiaomin and his colleagues, under the supervision of Dr. LIU Xiaolong find that Klf4 is the only reprogramming factor whose expression is down-regulated when early thymic progenitors differentiate into T cells. Enforced expression of Klf4 in uncommitted progenitors severely impaired T cell development mainly at the DN2-to-DN3 transition when T cell lineage commitment occurs, and affected the transcription of a variety of genes with crucial functions in early T cell development. The survival of thymocytes and the rearrangement at the Tcrb locus were impaired in the presence of enforced Klf4 expression. The defects in the DN1-to-DN2 and DN2-to-DN3 transitions in Klf4 transgenic mice could not be rescued by the introduction of a TCR transgene but was partially rescued by restoring the expression of IL-7Rα. Thus, these data suggest that the down-regulation of Klf4 is a prerequisite for T cell lineage commitment.

 

This research entitled “Down-regulation of the transcription factor KLF4 is required for the lineage commitment of T cells” was published online in Cell Research on Nov 22, 2011.

 

This work was supported in part by the Ministry of Science and Technology, the National Natural Science Foundation of China, and the Shanghai Municipal Government.

 

AUTHOR CONTACT:

LIU Xiaolong

State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.

Fax: +86-21-54921178, E-mail address: liux@sibs.ac.cn