小鼠胚胎干细胞自我更新的信号调控机制【摘要】 小鼠胚胎干细胞是一种全能干细胞，具有体内体外全能分化特性。体外培育时能够进行自我更新，即细胞通过对称分裂在维持全能性不丢失的情况下细胞数目增多。全能性维持受多条信号通路的调控，其中 gp130 下游的 JAK-STAT3 及PI3K 通路的活化能维持胚胎干细胞的自我更新，而 SHP2-Ras-ERK 的激活则促使胚胎干细胞分化。无血清条件下 BMP4 激活的通路与 JAK-STAT3 联合作用可保持胚胎干细胞的全能性。此外，Wnt 信号通路的活化也参加对胚胎干细胞的自我更新的调控。总之，多种信号通路形成的网络精确调控小鼠胚胎干细胞的自我更新与分化。本文主要综述 gp130 在小鼠 ES 细胞增殖过程中作用，包括 JAK-STAT3 通路活化抑制小鼠 ES细胞分化，PI3K 通路活化维持 ES 细胞的自我更新和 SHP-2-Ras 通路活化促进 ES 细胞分化，以及其他信号通路对小鼠 ES 细胞自我更新的影响，包括无血清条件下 BMP 联合 LIF 能维持 ES 细胞的高度自我更新，Wnt信号通路活化促进 ES 细胞自我更新。【关键词】 胚胎干细胞 自我更新 信号通路 全能性 Signaling Pathways Regulating Self-renewal of Mouse Embryonic Stem Cells —— Review AbstractMouse 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, , 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...
