Mouse Embryonic Stem Cell Pluripotency
ESC self-renewal and pluripotency in mouse are regulated by extrinsic and intrinsic factors. Extrinsic factors include LIF, BMP and WNT while the intrinsic machinery includes the transcription factors Oct4, Nanog and SOX2. LIF signaling is a major pathway contributing to mouse ESC pluripotency. LIF signals through the heterodimerization of LIFR and GP130 receptors. On binding LIF, the LIFR-GP130 heterodimer recruits JAK to phosphorylate STAT3...
Pathway Summary
ESC self-renewal and pluripotency in mouse are regulated by extrinsic and intrinsic factors. Extrinsic factors include LIF, BMP and WNT while the intrinsic machinery includes the transcription factors Oct4, Nanog and SOX2. LIF signaling is a major pathway contributing to mouse ESC pluripotency. LIF signals through the heterodimerization of LIFR and GP130 receptors. On binding LIF, the LIFR-GP130 heterodimer recruits JAK to phosphorylate STAT3. Phosphorylated STAT3 translocates to the nucleus and induces Oct4 and c-Myc transcription. LIF also activates the Ras/ERK signaling pathway through the effector protein SHP2. LIF-induced STAT3 activation promotes self-renewal, whereas LIF-induced ERK activation promotes differentiation. Phosphorylated JAK also activates the PI3K/AKT pathway which can also be activated endogenously by Eras.BMP4 is another extrinsic factor known to support mouse ESC self-renewal. In the presence of LIF, BMP4 activates the SMAD transcription factors. BMP4 binds to its receptor complex (BMPRII-ALK3) through which it induces the phosphorylation of SMAD1 and SMAD5. These phosphorylated SMADs then form a complex with SMAD4 and translocate into the nucleus to activate transcription of ID genes known to be involved in cell fate determination. ALK3 also dephosphorylates p38 MAPK and ERK and inactivates them. In the absence of LIF, low concentrations of BMPs promote mesoderm differentiation of mouse ES cells. In the presence of LIF, activated STAT3 interacts with T and causes up regulation of Nanog, leading to pluripotency.The canonical WNT pathway is activated on binding of WNT to the Frizzled receptor, which leads to inhibition of GSK3β. Subsequent nuclear accumulation of CTNN-β is followed by its association with LEF/TCF and CBP, and causes expression of target genes such as c-Myc, Oct4, Rex1 and STAT5, all critical for stem cell proliferation. GSK3β also negatively regulates c-Myc activity by phosphorylation and subsequent degradation by the proteasome system. Thus, extrinsic and intrinsic factors work together to determine mouse ESC renewal and pluripotency.
Mouse Embryonic Stem Cell Pluripotency Genes list
Explore Genes related to Mouse Embryonic Stem Cell Pluripotency
AKT1AKT serine/threonine kinase 1 AKT2AKT serine/threonine kinase 2 AKT3AKT serine/threonine kinase 3 APCAPC regulator of WNT signaling pathway APC2APC regulator of WNT signaling pathway 2 AXIN1axin 1 BMP4bone morphogenetic protein 4 BMPR1Abone morphogenetic protein receptor type 1A BMPR2bone morphogenetic protein receptor type 2 CREBBPCREB binding protein CTNNB1catenin beta 1 DVL1dishevelled segment polarity protein 1 DVL2dishevelled segment polarity protein 2 DVL3dishevelled segment polarity protein 3 ERASES cell expressed Ras FOXD3forkhead box D3 FZD1frizzled class receptor 1 FZD10frizzled class receptor 10 FZD2frizzled class receptor 2 FZD3frizzled class receptor 3 FZD4frizzled class receptor 4 FZD5frizzled class receptor 5 FZD6frizzled class receptor 6 FZD7frizzled class receptor 7 FZD8frizzled class receptor 8 FZD9frizzled class receptor 9 GRB2growth factor receptor bound protein 2 GSK3Bglycogen synthase kinase 3 beta HNF1AHNF1 homeobox A HRASHRas proto-oncogene, GTPase ID1inhibitor of DNA binding 1, HLH protein ID2inhibitor of DNA binding 2 ID3inhibitor of DNA binding 3, HLH protein ID4inhibitor of DNA binding 4, HLH protein IL6STinterleukin 6 signal transducer JAK1Janus kinase 1 JAK2Janus kinase 2 JAK3Janus kinase 3 KRASKRAS proto-oncogene, GTPase LEF1lymphoid enhancer binding factor 1 LIFLIF interleukin 6 family cytokine LIFRLIF receptor subunit alpha MAP2K1mitogen-activated protein kinase kinase 1 MAP2K2mitogen-activated protein kinase kinase 2 MAP3K7mitogen-activated protein kinase kinase kinase 7 MAPK1mitogen-activated protein kinase 1 MAPK11mitogen-activated protein kinase 11 MAPK12mitogen-activated protein kinase 12 MAPK13mitogen-activated protein kinase 13 MAPK14mitogen-activated protein kinase 14 MAPK3mitogen-activated protein kinase 3 MRASmuscle RAS oncogene homolog MYCMYC proto-oncogene, bHLH transcription factor NANOGNanog homeobox NRASNRAS proto-oncogene, GTPase PIK3C2Aphosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha PIK3C2Bphosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 beta PIK3C2Gphosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 gamma PIK3C3phosphatidylinositol 3-kinase catalytic subunit type 3 PIK3CAphosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha PIK3CBphosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta PIK3CDphosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta PIK3CGphosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma PIK3R1phosphoinositide-3-kinase regulatory subunit 1 PIK3R2phosphoinositide-3-kinase regulatory subunit 2 PIK3R3phosphoinositide-3-kinase regulatory subunit 3 PIK3R4phosphoinositide-3-kinase regulatory subunit 4 PIK3R5phosphoinositide-3-kinase regulatory subunit 5 PIK3R6phosphoinositide-3-kinase regulatory subunit 6 POU5F1POU class 5 homeobox 1 PTPN11protein tyrosine phosphatase non-receptor type 11 RAF1Raf-1 proto-oncogene, serine/threonine kinase RALARAS like proto-oncogene A RALBRAS like proto-oncogene B RAP1ARAP1A, member of RAS oncogene family RAP1BRAP1B, member of RAS oncogene family RAP2ARAP2A, member of RAS oncogene family RAP2BRAP2B, member of RAS oncogene family RASD1ras related dexamethasone induced 1 RASD2RASD family member 2 RRASRAS related RRAS2RAS related 2 SMAD1SMAD family member 1 SMAD4SMAD family member 4 SMAD5SMAD family member 5 SMAD9SMAD family member 9 SMOsmoothened, frizzled class receptor SOS1SOS Ras/Rac guanine nucleotide exchange factor 1 SOS2SOS Ras/Rho guanine nucleotide exchange factor 2 SOX2SRY-box transcription factor 2 STAT3signal transducer and activator of transcription 3 TAB1TGF-beta activated kinase 1 (MAP3K7) binding protein 1 TBXTT-box transcription factor T TCF3transcription factor 3 TCF4transcription factor 4 TCF7transcription factor 7 TCF7L1transcription factor 7 like 1 TCF7L2transcription factor 7 like 2 TP53tumor protein p53 TYK2tyrosine kinase 2 WNT3AWnt family member 3A XIAPX-linked inhibitor of apoptosis ZFP42ZFP42 zinc finger protein
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