中国学者发现上胚层干细胞分化为外胚层前体细胞的新机制

　　

　　5月19日，国际学术期刊Journal of Molecular Cell Biology 在线发表了中国科学院上海生命科学研究院生物化学与细胞生物学研究所景乃禾研究组的最新研究成果Ectodermal progenitors derived from epiblast stem cells by inhibition of Nodal signaling。该论文发现，通过抑制Nodal或FGF信号，可将上胚层干细胞分化为外胚层前体细胞。

　　近年来，多能干细胞向特定细胞谱系分化的应用前景，使得其分化机制研究成为生命科学与医学领域的热点。多能干细胞向外胚层、中胚层和内胚层等三胚层分化发育的正确起始，是生物个体生长发育的重要基础和前提。然而，多能干细胞是如何向外胚层分化的这一科学问题至今尚未很好解答。

　　景乃禾研究组李凌宇和宋璐的研究发现，在上胚层干细胞（EpiSCs）的体外分化中，通过短时间加入Nodal信号的抑制分子SB431542，可使细胞处于外胚层样细胞的状态。这种外胚层样细胞具有在体外分化为神经外胚层和表皮外胚层的潜能，而不能分化为中胚层和内胚层。进一步研究发现，抑制FGF信号也可以得到外胚层样细胞，并且这种细胞高表达Eras等标记基因。这项研究成果揭示了多潜能上胚层干细胞的体外分化过程经过外胚层干细胞阶段，并筛选到可能的外胚层标记基因。这一发现为干细胞向外胚层细胞的定向分化及其在再生医学中的应用提供了坚实的理论基础。

　　该项研究工作与加拿大病孩医院教授Janet Rossant合作完成，得到科技部、国家自然科学基金委和中科院干细胞先导专项等基金资助。

上胚层干细胞分化过程中通过抑Nodal或FGF获得外胚层样细胞

 

原文摘要：

Ectodermal progenitors derived from epiblast stem cells by inhibition of Nodal signaling

The ectoderm has the capability to generate epidermis and neuroectoderm and plays imperative roles during the early embryonic development. Our recent study uncovered a region with ectodermal progenitor potential in mouse embryo at embryonic day 7.0 and revealed that Nodal inhibition is essential for its formation. Here, we demonstrate that through brief inhibition of Nodal signaling in vitro, mouse embryonic stem cell (ESC)-derived epiblast stem cells (ESD-EpiSCs) could be committed to transient ectodermal progenitor populations, which possess the ability to give rise to neural or epidermal ectoderm in the absence or presence of BMP4, respectively. Mechanistic studies reveal that BMP4 recruits distinct transcriptional targets in ESD-EpiSCs and ectoderm-like cells. Furthermore, FGF–Erk signaling may also be alleviated during the generation of ectoderm-like cells. Thus, our data suggest that instructive interactions among several extracellular signals participate in the commitment of ectoderm from ESD-EpiSCs, which shed new light on the understanding of the formation of ectoderm during the gastrulation in early mouse embryo development.