Zhejiang Key Laboratory of Organ Development and Regeneration, College of Life and Environmental Sciences, Hangzhou Normal University, Zhejiang, 311121, China.
Zhejiang Key Laboratory of Organ Development and Regeneration, College of Life and Environmental Sciences, Hangzhou Normal University, Zhejiang, 311121, China; Institute of Cancer Stem Cell, Dalian Medical University, Dalian, 116044, China.
Biochem Biophys Res Commun. 2022 Apr 9;599:156-163. doi: 10.1016/j.bbrc.2022.02.002. Epub 2022 Feb 5.
Primitive Endoderm (PrE) is an extraembryonic structure derived from inner cell mass (ICM) in the blastocysts. Its interaction with the epiblast is critical to sustain embryonic growth and embryonic pattern. In this study, we reported a simple and efficient method to induce the differentiation of mouse Embryonic Stem Cells (mESCs) into PrE cells. In the process of ESC monolayer adherent culture, 1 μM atRA and 10 μM CHIR inducers were used to activate RA and Wnt signaling pathways respectively. After 9 days of differentiation, the proportion of PrE cells was up to 85%. Further studies indicated that Wnt signaling pathway acted as a switch that RA induces mESCs differentiation between SMC and PrE cell. In the presence of only RA signaling, mESCs adopted the fate of smooth muscle cells (SMCs); Simultaneous activation of the Wnt signaling pathway changed the differentiation fate of mESCs into PrE cells. This efficient induction method can provide new cellular resources and models for relevant studies of PrE.
原始内胚层（PrE）是由囊胚中的内细胞团（ICM）衍生而来的一种胚胎外结构。它与上胚层的相互作用对于维持胚胎生长和胚胎模式至关重要。在这项研究中，我们报道了一种简单有效的方法，可诱导小鼠胚胎干细胞（mESC）分化为原始内胚层细胞。在 ESC 单层贴壁培养过程中，分别使用 1μM 的全反式视黄酸（atRA）和 10μM CHIR 诱导剂激活 RA 和 Wnt 信号通路。经过 9 天的分化，PrE 细胞的比例达到 85%。进一步的研究表明，Wnt 信号通路作为一个开关，控制 RA 诱导 mESC 在平滑肌细胞（SMCs）和原始内胚层细胞之间的分化。仅存在 RA 信号时，mESC 会选择平滑肌细胞（SMCs）的命运；同时激活 Wnt 信号通路会改变 mESC 的分化命运为原始内胚层细胞。这种高效的诱导方法可为原始内胚层的相关研究提供新的细胞资源和模型。
