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Description FIGURE 7 Cell signalling events that mediate the switch between self-renewal and differentiation in mouse embryonic stem cells. (A) LIF binds to the LIF receptor (LIFR) resulting in heterodimerisation with glycoprotein-130 (gp130). Downstream JAK proteins become phosphorylated, and in this active state phosphorylate tyrosine residues on the receptor complex. STAT3 can then dock to the receptor, is then phosphorylated at Y705, and homodimerises before translocating to the nucleus where it induces the transcription of self-renewal genes. LIF also activates the PI3K pathway, in which PIP2 is converted to PIP3 resulting in the downstream phosphorylation of AKT at S473 and T308. This enhances self-renewal by upregulating the expression of Nanog, and by promoting cell cycle progression. (B) BMP4 binds to its cognate BMP receptor (BMPR) resulting in the phosphorylation of SMAD1/5/8. Once phosphorylated, SMAD1/5/8 forms heterodimers with SMAD4, which translocate to the nucleus resulting in transcription of inhibitor-of-differentiation (Id) genes. SMAD signaling also results in the upregulation of the phosphatase DUSP9 which acts as a negative regulator of ERK, thereby inhibiting differentiation. (C) LIF also activates the MAPK/ERK pathway to promote differentiation in the face of maintaining self-renewal. The balance can be tipped toward differentiation by the presence of Fibroblast Growth Factor (FGF4), which upregulates the activity of the MAPK/ERK pathways, as does (D) L-proline. L-proline enters the cell via the Sodium-coupled Neutral Amino Acid Transporter (SNAT)-2 where it activates mTOR to induce the differentiation of mESCs to early primitive ectoderm-like (EPL) cells. Figure adapted from data published in: (Ying et al., 2003b; Paling et al., 2004; Binétruy et al., 2007; Washington et al., 2010; Hirai et al., 2011; Romero-Lanman et al., 2012; Hamilton and Brickman, 2014)
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Source https://www.researchgate.net/publication/334407321_Modeling_Mammalian_Commitment_to_the_Neural_Lineage_Using_Embryos_and_Embryonic_Stem_CellsModeling_Mammalian_Commitment_to_the_Neural_Lineage_Using_Embryos_and_Embryonic_Stem_Cells Modeling Mammalian Commitment to the Neural Lineage Using Embryos and Embryonic Stem Cells. July 2019. Frontiers in Physiology 10 DOI:10.3389/fphys.2019.00705
Author Rachel A. Shparberg, Hannah J. Glover, Michael B. Morris
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current19:06, 30 April 2024Thumbnail for version as of 19:06, 30 April 20241,198 × 873 (257 KB)Rasbak (talk | contribs){{Information |description=FIGURE 7 Cell signalling events that mediate the switch between self-renewal and differentiation in mouse embryonic stem cells. (A) LIF binds to the LIF receptor (LIFR) resulting in heterodimerisation with glycoprotein-130 (gp130). Downstream JAK proteins become phosphorylated, and in this active state phosphorylate tyrosine residues on the receptor complex. STAT3 can then dock to the receptor, is then phosphorylated at Y705, and homodimerises before translocating t...

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