信号转导学院 - 赢在信号通路

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通路描述：

Two distinguishing characteristics of embryonic stem cells (ESCs) are pluripotency and the ability to self-renew. These traits, which allow ESCs to grow into any cell type in.the adult body and divide continuously in the undifferentiated state, are regulated by a number of cell signaling pathways. In human ESCs (hESCs), the predominant signaling pathways involved in pluripotency and self-renewal are TGF-β, which signals through Smad2/3/4, and FGFR, which activates the MAPK and Akt pathways. The Wnt pathway also promotes pluripotency, although this may occur through a non-canonical mechanism involving a balance between the transcriptional activator, TCF1, and the repressor, TCF3. Signaling through these pathways supports the pluripotent state, which relies predominantly upon three key transcription factors: Oct-4, Sox2, and Nanog. These transcription factors activate gene expression of ESC-specific genes, regulate their own expression, suppress genes involved in differentiation, and also serve as hESCs markers. Other markers used to identify hESCs are the cell surface glycolipid SSEA3/4, and glycoproteins TRA-1-60 and TRA-1-81. In vitro, hESCs can be coaxed into derivatives of the three primary germ layers, endoderm, mesoderm, or ectoderm, as well as primordial germ cell-like cells. One of the primary signaling pathways responsible for this process is the BMP pathway, which uses Smad1/5/9 to promote differentiation by both inhibiting expression of Nanog, as well as activating the expression of differentiation-specific genes. Notch also plays a role in differentiation through the notch intracellular domain (NICD). As differentiation continues, cells from each primary germ layer further differentiate along lineage-specific pathways.

主要文献：

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