中国生物工程杂志

Embryonic stem (ES) cells derived from the inner cell mass(ICM) of the blastocyst, which can proliferate indefinitely in vitro(self-renewal) and can differentite into cells of all three germ layers(pluripotency). These unique properties make them exceptionally valuable for cell replacement therapies drug discovery and regenerative medicine. However, as for organ transplants, tissue rejection remains a significant concern for ES cell transplantation. Another concern is the use of human embryos. One possible means to avoid these issues is by reprogramming the nuclei of differentiated cells to ES cell-like, pluripotent cells. Several extrinsic signals such as LIF, BMP and Wnt can support the self-renewal and pluripotency of embryonic stem (ES) cells through regulating the "pluripotent genes." A unique homeobox transcription factor, Nanog, is one of the key downstream effectors of these signals. Elevated level of Nanog can maintain the mouse ES cell self-renewal independent of LIF and enable human ES cell growth without feeder cells. In addition to the external signal pathways, intrinsic transcription factors such as FoxD3, P53,Tcf3 and Oct4 are also involved in regulating the expression of Nanog. Functionally, Nanog works together with other key pluripotent factors such as Oct4 and Sox2 to control a set of target genes that have important functions in maintenancing ES cell pluripotency. These key factors form a regulatory network to support or limit each other's expression level, which maintains the properties of ES cells.