Laboratory of Embryo Biotechnology, College of Life Science, Northeast Agricultural University, Harbin, China.
School of Life Sciences, Westlake University, Hangzhou, China.
Cell Prolif. 2020 Apr;53(4):e12782. doi: 10.1111/cpr.12782. Epub 2020 Mar 20.
Extraembryonic endoderm (XEN) cells are isolated from primitive endoderm (PrE) of blastocysts. Just like PrE, XEN cells have the ability to differentiate into parietal endoderm (PE) and visceral endoderm (VE), and therefore, they are useful tools for studying mechanisms of PrE cells development and differentiation. Pig is an ideal model for studying human cardiovascular and metabolic diseases and a potential organ source for allotransplantation, while no XEN cell has been obtained from porcine embryos.
Using a serum-free culture system, we directly derived porcine extraembryonic endoderm-like cells (pXEN-like cells) from day 6-7 blastocysts, which could maintain self-renewal for at least 30 passages.
The pXEN-like cells resembled mouse XEN cells with large and flat clone morphology and expressed XEN marker genes but not pluripotent genes. Upon in vitro induction, the cells could differentiate into VE and PE. FGF/MEK signalling was not only essential for the maintenance of pXEN-like cells, but also the induction of pXEN-like cells from porcine embryonic stem (pES) cells.
We directly obtained cell lines with XEN characteristics from porcine embryos for the first time. The cells will be helpful tools for studying embryonic development and cell differentiation, which also represent promising cell sources for human regenerative medicine.
胚外内胚层(XEN)细胞从囊胚的原始内胚层(PrE)中分离得到。与 PrE 一样,XEN 细胞具有分化为滋养内胚层(PE)和内脏内胚层(VE)的能力,因此它们是研究 PrE 细胞发育和分化机制的有用工具。猪是研究人类心血管和代谢疾病的理想模型,也是同种异体移植的潜在器官来源,而尚未从猪胚胎中获得 XEN 细胞。
我们使用无血清培养系统,直接从第 6-7 天的囊胚中获得猪胚外内胚层样细胞(pXEN 样细胞),这些细胞至少可以自我更新 30 代。
pXEN 样细胞与小鼠 XEN 细胞相似,具有大而扁平的克隆形态,并表达 XEN 标记基因,但不表达多能基因。在体外诱导下,这些细胞可分化为 VE 和 PE。FGF/MEK 信号通路不仅对 pXEN 样细胞的维持至关重要,而且对猪胚胎干细胞(pES)向 pXEN 样细胞的诱导也至关重要。
我们首次直接从猪胚胎中获得具有 XEN 特征的细胞系。这些细胞将成为研究胚胎发育和细胞分化的有用工具,也代表了人类再生医学有前途的细胞来源。