LU Rui and colleagues in the Key Laboratory of Stem Cell Biology (JIN Ying, group director), Institute of Health Sciences, Shanghai Institutes for Biological Sciences, CAS have revealed a dual functional role of Tbx3, a pluripotency-related transcription factor of the T-box gene family, for determination of ESC fate. In an article published in The Journal of Biological Chemistry, the group reports that this factor is required for both the maintenance of self-renewal of mouse ESCs and for their differentiation into extraembryonic endoderm (ExEn).

The study started from showing that Tbx3 is highly expressed in ExEn cells in addition to undifferentiated ESCs, suggesting a potential role of Tbx3 in ExEn development. Knockdown of Tbx3 expression using tetracycline-regulated Tbx3 siRNA resulted in the attenuation of ESC self-renewal ability and aberrant differentiation processes, including reduced ExEn differentiation but enhanced ectoderm and trophectoderm differentiation. Conversely, inducible forced expression of Tbx3 triggered ExEn lineage commitment. Mechanistically, Tbx3 directly activated the expression of Gata6, an essential regulator of ExEn. Interestingly, Tbx3 modulated H3K27me3 modification and the association of the PRC2 complex with the promoter region of Gata6. Taken together, the results of this study revealed a previously unappreciated role of a pluripotency factor in ExEn differentiation. Additionally, the study reveals that Tbx3 may function through direct binding and epigenetic modification of histones on the Gata6 promoter to maintain the ExEn differentiation potential of ESCs. This set of findings provides new insight into the potential “bifunctional role” of the pluripotency factors in the usual sense.

This work entitled “Dual Functions of T-Box 3 (Tbx3) in the Control of Self-renewal and Extraembryonic Endoderm Differentiation in Mouse Embryonic Stem Cells” was publishedin The Journal of Biological Chemistry on Mar 11, 2011.

This work was supported by the National Natural Science Foundation Grants, the National High Technology Research and Development Program of China Grants, and the Shanghai Science and Technology Developmental Foundations Grant. The work was also supported by the Shanghai Leading Academic Discipline Project.

AUTHOR CONTACT:
JIN Ying
The Institute of Health Sciences,
Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences,
& Shanghai Jiao Tong University School of Medicine
Shanghai, China
Phone: 86-21-63852591; E-mail: yjin@sibs.ac.cn