1. Department of Obstetrics and Gynecology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
2. Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan
3. Department of Occupational Medicine, Hualien Tzu Chi Hospital; Tzu Chi University, Hualien, Taiwan
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 in vitro and in vivo 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 in vitro.
Keywords: induced pluripotent stem cells, embryo, dedifferentiation, endometrial polyp, cervical polyp