Signaling pathways regulating self-renewal of mouse embryonic stem cells--review / 中国实验血液学杂志

ABSTRACT

Mouse embryonic stem cells (ES cells) are pluripotent in that they can give rise to almost all the cell types in vitro and in vivo. Also, they can sustain self-renewal in vitro owing to symmetrical mitosis, i.e., only the cell number increases while the daughter cells remain pluripotent. Self-renewal and pluripotency of ES cells are under stringent regulation of several signaling pathways. Activation of either JAK-STAT3 or PI3K, the downstream cascade of gp130, can maintain the self-renewal of ES cells, while phosphorylation of another gp130-related branch, SHP2-Ras-ERK, drives the differentiation. BMP2/4-mediated signaling is capable of suppressing the differentiation of ES cells in collaboration with activated JAK-STAT3 under serum free culture conditions. Other signaling such as Wnt also contributes to the self-renewal of ES cells. Generally, the network, which is composed of various signaling pathways, modulates the self-renewal and differentiation of mouse ES cells precisely. This review focuses on the role of gp130 in proliferation of mouse ES cells including inhibitory effect of JAK-STAT3 pathway activation on differentiation of mouse ES cells, maintenance effect of PI3K pathway activation on self-renewal of ES cells, promotive effect of SHP-2-Ras-ERK pathway activation on differentiation of ES cells, and influence of other signaling pathways on self-renewal of mouse ES cells, including maintenance effect of BMP combination with LIF under serum free culture conditions on self-renewal of ES cells and promotive effect of Wnt pathway activation on self-renewal of ES cells.