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- 积分
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The signaling pathways controlling pluripotent stem cell self-renewal. mES cells can be maintained by LIF and BMP, while hES cells self-renew under bFGF and Activin A. Wnt/b-catenin, PI3K, LIF/STAT3, BMP4/Smad1/5 signaling pathways play critical roles in maintaining mES cell self-renewal. Wnt signaling entails inhibition of GSK3b and protein stabilization of cytoplasmic b-catenin (b-Ctnn). GSK3 inhibitor CHIR99021 prevents the phosphorylation of b-Ctnn by GSK3b and activates Wnt signaling. The target genes of Wnt signaling pathway, such as c-Myc and CyclinD1, can promote cell proliferation and self-renewal. PI3K activity, enhancing cell
: o% J% X; z( r7 o, uproliferation and survival as well as inhibiting apoptosis, is also crucial for self-renewal of ES cells. The growth factors and cytokines, such as bFGF and LIF, can activate PI3K signaling. LIF also drives self-renewal of mES cells by activating the STAT3. But LIF activates MAPK/ERK pathway too, which induces mES cell differentiation. MEK inhibitor PD0325901 can inhibit the MAPK/ERK signaling pathway to promote mES cell self-renewal. Pluripotin can activate PI3K (by inhibiting RasGAP) and inhibit ERK to sustain mES cell self-renewal. BMP4/Smad1/5 signaling also supports mES cell self-renewal by inhibiting MAPK/ERK signaling pathway and induces the expression of Id
: z6 H3 j. C$ a4 r3 I(inhibitor of differentiation) protein. TGFb/Activin A pathway has contextual effects on promoting self-renewal of hES cells in conjunction with bFGF, or inducing endoderm differentiation of m/hES cells. |
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发表于 2011-12-3 22:34
发表于 2011-12-4 09:29
