Department of Obstetrics and Gynecology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan.
Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan.
Int J Biol Sci. 2018 Sep 7;14(11):1586-1598. doi: 10.7150/ijbs.23401. eCollection 2018.
By introduction of Oct4, Sox2, Klf4 and cMyc, human adult somatic cells can be reprogrammed into embryonic stem cell capable of pluripotent differentiation. In several lines of human endometrial polyp- and cervical polyp-mesenchymal stem cells (EPMSCs and CPMSC), we showed introduction of the four transcription factors led to a dedifferentiation of these cells into early embryo-like cells in three days, ranging from one-cell, two-cell, four-cell embryos, and morula to blastocyst. These early embryo-like cells resembled human early embryo derived from in vitro fertilization (IVF) in morphology, and hatching activity. These cells also expressed hypoblast (GATA4) and trophoblast (Cdx2) markers. After culturing the embryo-like cells for one month, the induced pluripotency stem cells (iPSC) could be formed (proved by pluripotency gene expression, by and differentiation). C/EBPα expression was also increased in uterine polyps. In contrast, MSCs derived from normal endometrium could not be induced to dedifferentiation to such early embryo-like cells. We conclude that EPMSCs and CPMSCs could be dedifferentiated to early embryo-like cells by the iPSC cocktail. This suggests that polyps of the organ derived from Mullerian duct may harbor epigenetic markers making them vulnerable to reprogramming to the earliest developmental stage. This study provides a simple model to derive early human embryo-like cells by .
通过引入 Oct4、Sox2、Klf4 和 cMyc,人类成体细胞可以被重编程为具有多能性分化能力的胚胎干细胞。在几条人子宫内膜息肉和宫颈息肉间充质干细胞 (EPMSC 和 CPMSC) 中,我们表明,引入这四个转录因子可使这些细胞在三天内分化为类似早期胚胎的细胞,从单细胞、二细胞、四细胞胚胎到桑葚胚和囊胚。这些类似早期胚胎的细胞在形态和孵化活性上类似于体外受精 (IVF) 获得的人早期胚胎。这些细胞还表达下胚层 (GATA4) 和滋养层 (Cdx2) 标志物。将类似早期胚胎的细胞培养一个月后,可形成诱导多能干细胞 (iPSC) (通过多能性基因表达和 和 分化证明)。C/EBPα 的表达也在子宫息肉中增加。相比之下,来源于正常子宫内膜的间充质干细胞不能被诱导分化为这种类似早期胚胎的细胞。我们得出结论,EPMSC 和 CPMSC 可以通过 iPSC 鸡尾酒被去分化为类似早期胚胎的细胞。这表明,来自 Müllerian 管的器官息肉可能具有使其易受重编程为最早发育阶段的表观遗传标记。本研究通过 提供了一种简单的模型来获得类似早期人类胚胎的细胞。