To study the property of pluripotent stem cells, Dr. SONG Lu and their colleagues from the lab of Prof. JING Naihe at Institute of Biochemistry and Cell Biology (SIBCB), Shanghai Institutes for Biological Sciences (SIBS) of Chinese Academy of Sciences found dynamic heterogeneity of brachyury in mouse epiblast stem cells. This work was recently published in The Journal of Biological Chemistry (JBC).

Mouse pluripotent cells such as embryonic stem cells (ESCs) and epiblast stem cells (EpiSCs) provide excellent in vitro systems to study imperative pre- and post-implantation events of in vivo mammalian development. It is known that ESCs are dynamic heterogeneous populations. However, it remains largely unclear whether and how EpiSCs possess similar heterogeneity and plasticity as ESCs. Furthermore, whether the oscillated expression of the pioneer lineage-biased genes could mediate differential responses of EpiSCs to the extrinsic signals remains unknown.

In this study, scientists established T-EpiSCs from T-GFP ESCs and found that T-EpiSCs have the T-positive and the T-negative subpopulations. Both of these two populations are pluripotent and could convert into each other. They revealed that the T-positive EpiSCs could readily contribute to the mesendoderm lineage. In contrast, the T-negative EpiSCs are biased toward the ectoderm cell fate. The T-positive and the T-negative subpopulations have different responses to bone morphogenetic protein (BMP) signaling, which enhances the generation of mesendoderm lineage in the T-positive cells, but promotes the epidermal differentiation in the T-negative subpopulation.

The mechanistic studies revealed that BMP4 ensures mesendoderm fate determination via Snail in T-positive EpiSCs, and accelerate epidermis lineage commitment through Id1 in T-negative cells. Furthermore, T gene also plays imperative roles in the EMT during EpiSC differentiation through regulating the expression of several functional factors. The discovery shed new light on the understanding of the property of epiblast stem cell.

The work was supported by grants from the Ministry of Science and Technology of China, the National Natural Science Foundation of China and Strategic Priority Research Program of Chinese Academy of Sciences.

Figure: Model for dynamic heterogeneity of T expression in mouse epiblast stem cells (Image by Prof. JING Naihe’s group)